Korean J Lab Med 2010;30: DOI /kjlm Review Article Diagnostic Immunology New HLA Nomenclature (2010) and Its Clinical Appli

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1 Korean J Lab Med 2010;30: DOI /kjlm Review Article Diagnostic Immunology New HLA Nomenclature (2010) and Its Clinical Application in Koreans Kyung Wha Lee, Ph.D. 1 and Myoung Hee Park, M.D. 2 Hallym Institution for Genome Application 1, Hallym University College of Medicine, Anyang; Department of Laboratory Medicine 2, Seoul National University College of Medicine, Seoul, Korea Human leukocyte antigen (HLA) gene region encodes a set of HLA molecules functioning critical roles in immune response. Each HLA gene locus shows extensive polymorphism with ever-increasing number of alleles. The HLA nomenclature system for alleles defined by DNA typing was first established in 1987 and has been revised several times. Recently, it has been revised again with a new frame that can accommodate ever-increasing number of new alleles. The new system has also introduced the novel suffixes, P and G, to simplify reporting of ambiguous strings of alleles in typing reports. This review introduces the HLA nomenclature system-2010 in conjunction with its clinical application in Koreans. (Korean J Lab Med 2010;30:203-17) Key Words : Human leukocyte antigen, Nomenclature, Korean 서 Human leukocyte antigen (HLA) 은사람의유핵세포표면에발현되는세포막당단백분자로, T 림프구에항원을제시하여침입한항원에대한적응면역반응을유발시키고또한자연살해세포 (natural killer cell) 에의한사멸작용으로부터정상세포를보호하는기능을담당하고있다. 각개인에서발현되는 HLA 분자의형별은매우다양하며이제까지발견된사람의항원계중에서다형성 (polymorphism) 이가장높은것으로알려져있다. 다형성의특징과면역계에서의중요한기능때문에 HLA 분자는장기이식이나질병감수성의연구등임상분야에서매우중요하게인식되어왔다 [1]. 본종설에서는새롭게변경된 HLA DNA 명명법 (2010) 을소개하고한국인에서발견되는 HLA 대립유전자를중심으로새 Received : April 30, 2010 Manuscript No : KJLM Revision received : May 31, 2010 Accepted : May 31, 2010 Corresponding author : Kyung Wha Lee, Ph.D. Hallym Institution for Genome Application, Hallym University Sacred Heart Hospital and Hallym University College of Medicine, 896 Pyeongchon-dong, Dongan-gu, Anyang , Korea Tel : , Fax : leekw@hallym.or.kr ISSN 론 The Korean Society for Laboratory Medicine 명명법을쉽게적용할수있도록 Table로제시하고자한다. 또한, 대폭변경된명명법의이해를돕기위해이전명명법과의주요차이점도소개하고자한다. 이를통해 HLA 관련분야 (HLA 형별검사, 조혈모세포이식, 임상연구등 ) 종사자들이방대한내용의새로운 HLA 명명법에대해쉽게이해하고임상에적용할수있도록도움을주고자하였다. HLA의다형성규명 1. HLA 분자의발견및다형성규명 HLA 분자는유럽과미국의세연구팀에서수혈을여러번받은환자와임신경험이여러번있는경산부의혈청에다른사람의백혈구와반응하는여러가지항-백혈구항체가존재한다는연구결과를 1958년에각각보고함으로써그존재와다형성이인식되기시작했다 [2]. 보다체계적인연구수행과연구자간의연구결과를공유하기위하여 1964년에는세계각지로부터 23 명의관련연구자가미국의듀크대학에모여처음으로 국제 HLA 워크숍 (International Histocompatibility Workshop) 을개최하게되었으며, 그후 2-4년간격으로개최되어 제15 차국제 HLA 워크숍 (2008년개최 ) 에이르게되었다. 초기단 203

2 204 Korean J Lab Med 2010;30: 계의 국제 HLA 워크숍 에서가장큰문제점으로대두된것은항원의명칭문제였는데각연구실마다발견된 HLA 특이성에대해연구자가임의로이름을붙여사용함으로써연구결과의상호비교와해석에어려움이많다는것이었다. 이런문제점을해결하기위하여 HLA 특이성에대한명칭을표준화해야한다는인식이확산되면서 1968년에는세계보건기구산하에 WHO HLA 명명위원회 (WHO Nomenclature Committee for Factors of the HLA System) 를발족하게되었다 [3]. 이때부터각각의 HLA 특이성은첫보고후다른연구자에의해재확인된것들에대해서만일정한형식의명명이이루어지게되었다. 이와같은체계적인명명시스템으로전세계 HLA 분야에종사하고있는전문가들이각각의 HLA 형별에대한동일한표준명칭을사용할수있게된것이다. HLA 분자의혈청학적특이성규명에있어서초창기에인식되었던또다른문제점은 HLA 특이성을확인하기위해사용할수있는표준화된혈청이없어서각연구자가보유하고있는다양한특이성의항-HLA 혈청을이용하였다는것이다. 뿐만아니라적용하는분석방법도연구실마다다양하여 ( 백혈구응집법, leukoagglutination; 간접항글로불린소모법, indirect antiglobulin consumption test; 보체의존성세포독성법, complement dependent cytotoxicity) 결과해석과공유에어려움이많았었다. 이와같은혼란은 Terasaki와 McClelland [4] 에의해개발된 microdroplet assay 가이용되면서해소되기시작하여, 1970년대부터는보다체계적이고편리하게임상에서이용되어왔다. 이검사법은현재도사용되고있는표준혈청학적검사법으로특이성이다른수십개의항-HLA 혈청을한개의반응판 (reaction plate) 에점적하고보체의존성세포독성검사법으로 HLA 형별을판정하는방법이다. 2009년 12 월말까지 WHO HLA 명명위원회에의해명명된 HLA-A, -B, -C, -DR, -DQ 분자에대한혈청학적특이성의종류는 Table 1과같다 [5]. Table 1에함께열거된 HLA-DP 분자의특이성 (DPw1-DPw6) 은혈청학적검사법으로는검출이불가능하여 primed lymphocyte typing이라는림프구배양법으로검출된것이다. 2. HLA 유전자의다형성규명 1980년대부터시작된분자생물학의발달과함께인간염색체 6번의단완부에 HLA 유전자부위 (HLA gene region) 에는여러개의유전자좌 (gene locus) 가존재한다는것이밝혀졌으며, 현재까지 WHO HLA 명명위원회에의해규명된유전자좌 Table 1. List of recognized serological and cellular specificities by WHO HLA Nomenclature Committee (2010) HLA-A HLA-B HLA-B HLA-C HLA-DR HLA-DQ HLA-DP A1 B5 B51 (5) Cw1 DR1 DQ1 DPw1 A2 B7 B5102 Cw2 DR103 DQ2 DPw2 A203 B703 B5103 Cw3 DR2 DQ3 DPw3 A210 B8 B52 (5) Cw4 DR3 DQ4 DPw4 A3 B12 B53 Cw5 DR4 DQ5 (1) DPw5 A9 B13 B54 (22) Cw6 DR5 DQ6 (1) DPw6 A10 B14 B55 (22) Cw7 DR6 DQ7 (3) A11 B15 B56 (22) Cw8 DR7 DQ8 (3) A19 B16 B57 (17) Cw9 (w3) DR8 DQ9 (3) A23 (9) B17 B58 (17) Cw10 (w3) DR9 A24 (9) B18 B59 DR10 A2403 B21 B60 (40) DR11 (5) A25 (10) B22 B61 (40) DR12 (5) A26 (10) B27 B62 (15) DR13 (6) A28 B2708 B63 (15) DR14 (6) A29 (19) B35 B64 (14) DR1403 A30 (19) B37 B65 (14) DR1404 A31 (19) B38 (16) B67 DR15 (2) A32 (19) B39 (16) B70 DR16 (2) A33 (19) B3901 B71 (70) DR17 (3) A34 (10) B3902 B72 (70) DR18 (3) A36 B40 B73 A43 B4005 B75 (15) DR51 A66 (10) B41 B76 (15) DR52 A68 (28) B42 B77 (15) DR53 A69 (28) B44 (12) B78 A74 (19) B45 (12) B81 A80 B46 B82 B47 B48 Bw4 B49 (21) Bw6 B50 (21) Taken from the reference [5]. 는 50 개가넘는다 [5]. 그중장기이식과관련성이높은고전적의미의 HLA class I 유전자좌에는 3종 (HLA-A, -B, -C) 이있고, HLA class II 유전자좌에는 9종 (HLA-DRA, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, -DPB1) 이있다. 1990년대부터 HLA 유전자분석에중합효소연쇄반응기법 (polymerase chain reaction) 이도입되면서각유전자좌에대한염기서열분석이용이해졌다. 이로써 HLA 다형성이혈청학적수준에서보다유전자수준에서훨씬높다는사실이밝혀졌으며, 그규모는해가거듭됨에따라초기의예측을훨씬뛰어넘어 2009년 12월말까지명명된 class I과 class II의대립유전자수는각각 3,134개와 1,158개에달하고있다 (Table 2). 지난몇달간 WHO HLA 명명위원회에신규로등록된대립유전자들중에서이미대립유전자의수가 99개를초과한대립유전자군 ( 예. A*24, B*07, B*35, B*40, DRB1*13, DRB1*14) 에속

3 Lee KW, et al., New HLA Nomenclature (2010) 205 하는것들은새로운 HLA 명명법 (2010) 이공식적으로적용되는 2010년 4월이후로명명을유보해두었기때문에향후수개월내에명명되는대립유전자의수가폭증할것으로예상된다. 새로운 HLA 명명법 (2010) 의개요 1987년에처음도입된 HLA DNA 명명법 [6] 은그간 10 회에걸쳐개선작업이이루어져왔다. WHO HLA 명명위원회는 2008년 9월에브라질에서개최된 제15차국제 HLA 워크숍 기간에모임을갖고 HLA 명명과관련된여러가지쟁점에대한토론을가졌으며, 온라인상에서명명위원들간의추가토론을거친끝에새로운틀의명명법으로개선하게되었다. 2010년 4월부터공식적으로사용하기로결정된 HLA DNA 명명법-2010 에대한자세한정보는최근관련전문학술지에보고된바있으며 165쪽의방대한분량에달한다 [5]. 이에대한정보는 HLA Table 2. Number of alleles with official names at each HLA locus by 31st December 2009 HLA locus Selected from the reference [5]. N of alleles A 965 B 1,543 C 626 DRA 3 DRB1 762 DRB3 52 DRB4 14 DRB5 19 DQA1 35 DQB1 107 DPA1 28 DPB1 138 데이터베이스웹사이트 ( 와 HLA 명명웹사이트 (hla.alleles.org) 등에도제공되고있다 [7]. 이번에개정된명명법에기초한 HLA 명명의예는 Fig. 1과같다. 즉, HLA DNA 명명의기본구조 ( 예. A*01:01:01:02N) 는별표 (*) 를중심으로왼쪽에는대립유전자가규명된유전자좌 ( 예. A, B, C, DRB1, DQB1 등 ) 를기록하고오른쪽에는콜론 (:) 으로영역간의경계가표시된아라비아숫자들로표기되어있으며, 일부대립유전자에한하여오른쪽맨끝에한자리의알파벳접미사가붙어있다. 각영역의숫자는최소두자릿수는되어야하기때문에 Fig. 1과같이한자릿수형별을나타낼경우, 첫번째에는항상숫자 0 을넣어두자릿수로채워야한다. 콜론 (:) 에의해구분되는각영역의숫자와알파벳접미사의의미도각각다르다. 1. 콜론 ( : ) 으로구분되는각영역숫자의의미별표 (*) 직후에표기되는첫번째영역의숫자는혈청학적특이성이유사하거나혹은단순히염기서열의유사성이높은대립유전자군 (allele family) 을의미한다. 예를들어, A*01:02와 A*01:03은모두 A1 혈청학적특이성을나타내기때문에 A*01 대립유전자군에속하게되었다. 반면, 한국인에서발견되고있는 B*55:02:01과 B*55:07은각각혈청학적특이성이 B55와 B54 로서로다르지만 1개의염기서열차이 (45GAG>GGG, 45Glu> Gly) 만나타내기때문에 B*55 대립유전자군에속하게된것이다 [8]. 이영역의의미가혈청학적특이성의유사성에서염기서열의유사성으로확대된이유는유전자분석법의기술적발전에기인한다. 즉, HLA DNA 명명초기에는대부분의대립유전자에서유래된단백분자의혈청학적특이성도함께분석되었기 A*01:01:01:02N <definition and meaning of each field of the nomenclature> A...gene locus of the allele derived [HLA-A gene] *...delimiter between gene locus and allele designation 01...serologic type or allele family [allelic product carries A1 serologic type] 01...subtype in an allele family [firstly identified allele in the A*01 family] 01...variation with synonymous nucleotide substitutions [firstly identified allele in the A*01:01 subfamily] 02...variation with nucleotide substitutions in non-coding region only [secondly identified allele in the A*01:01:01 subfamily] N...information on allele expression [not expressed on the cell surface] Fig. 1. Example of an name with description (Nomenclature-2010). Illustration in bracket [ ] provides information on each field of the nomenclature, A*01:01:01:02N.

4 206 Korean J Lab Med 2010;30: 때문에대립유전자의염기서열과혈청학적특이성의상호연관성이잘규명되었다. 그러나, 유전자증폭기법과 DNA 염기서열분석기법의발달과함께혈청학적형별의특이성에대한정보없이보고되는대립유전자의수가폭증하면서 1996년명명법부터첫두자리숫자는단순히염기서열의유사성을의미하게된것이다 [9]. 별표 (*) 후두번째영역의숫자는동일한대립유전자군에속하는것으로 exon 부위에소규모 (1개-수개 ) 의아미노산변이를동반하는염기서열차이를나타낸대립유전자들의발견순서를의미한다. 예를들어, B*55:02:01과 B*55:07은 B*55 대립유전자군에속하는것들로각각두번째와일곱번째로발견된것이며앞에서기술한것과같이서로 1개의아미노산차이를나타낸다. 별표 (*) 후세번째영역의숫자는동일한대립유전자군에속하는것으로 exon 부위에염기서열차이를나타내지만아미노산서열에는변화가없는동일계염기치환 (synonymous nucleotide substitution) 을나타내는대립유전자들의발견순서를의미한다. 예를들어, A*01:01:02와 A*01:01:03은 A*01:01 대립유전자군에서각각두번째와세번째로발견된것으로서로 1개의염기서열차이를보이지만 (142ATT>ATC) 아미노산서열 (142Ile) 에는차이가없는것들이다. 별표 (*) 후네번째영역의숫자는아미노산으로코딩되지않는부위 (intron, 5 - untranslated region, 3 -untranslated region) 의염기서열에변이를나타내는대립유전자들의발견순서를의미한다. 예를들어, A*03:01:01:01과 A*03:01:01:03은 exon 부위의염기서열은동일하지만 intron 2에 1개의염기서열차이 (19G>T) 를나타내는것들로, 각각첫번째와세번째로발견된 A*03:01:01 군의대립유전자들이다. 2. 알파벳접미사 N, L, S, Q의의미마지막으로알파벳대문자접미사는유전자의비정상적인발현에대한추가정보를제공한다. 즉, 정상적인 HLA 대립유전자는세포표면에정상적으로발현되지만일부대립유전자들은특이한염기서열변이를갖고있기때문에발현양상이정상적이지못하다. 예를들어, 단백분자로전혀발현되지않는대립유전자에는 null 을상징하는접미사 N ( 예. A*24:09N) 을, 정상대립유전자와비교하여세포표면에의발현량이극히적은대립유전자는 low 를의미하는접미사 L ( 예. A*24:02:01: 02L) 을, 유전자는발현되지만세포표면에발현되지않고세포밖으로분비되는대립유전자에는 soluble 을상징하는 S ( 예. B*44:02:01:02S) 를추가한다. 그리고세포표면에서의발현에 중대한영향을미치는염기서열변이를갖고있지만, 유전자발현양상이단백분자수준에서직접확인되지않았기때문에확실한결론을내리지못한대립유전자에는 questionable 을의미하는 Q ( 예. A*32:11Q) 를추가한다. 3. HLA 대립유전자명칭의임상적용 HLA 대립유전자의명칭에서 1영역과 2영역의숫자가하나라도다른대립유전자들은아미노산서열이다른것들이며, 3-4영역의숫자가다르더라도 1-2영역의숫자가동일한대립유전자들은아미노산서열이동일한것들이다. 장기이식등을위한임상검사에서는 HLA 분자의항원결합부위를중심으로한아미노산서열정보가기능에중요한영향을미치기때문에명명의 1-2영역까지만표기해주는경우가많다. 그러나, 1-2영역에서숫자가동일하더라도명명끝부분에 N 의접미사가붙은대립유전자들은단백분자로발현되지않는것이므로동일한아미노산서열을나타내는대립유전자라고할수없다. 환자와기증자간에 HLA 형별일치여부가이식의결과에큰영향을미치는조혈모세포이식에서는이들 N 의접미사가붙은대립유전자들을정확히구분하여보고하는것이필요하다 [10]. 4. HLA 대립유전자와단백분자표기의차이 동일한 HLA 명명에대하여대립유전자로표기해야할경우가대부분이지만, 해당대립유전자의산물인단백분자로표기해야할경우도간혹있을수있다. 이를인식하여 WHO HLA 명명위원회에서는이들두가지에대한표기법을다르게하도록하였다. 즉, 대립유전자명명은이탤릭체대문자 ( 예. A*01:01: 01:01) 로표기하고단백분자명명은이탤릭체를사용하지않는다 ( 예. A*01:01:01:01). 한국인에존재하는 HLA 형별에대한새로운 HLA 명명법 (2010) 의적용 각각의 HLA 유전자좌에대하여수십에서수천개가넘는대립유전자가보고되었으나, 각인종에서발견되는대립유전자의수는이들중극히일부에불과한것으로알려졌다. 각인종에존재하는 HLA 대립유전자의수는인종의다양성에비례하기때문에다양성이매우높은것으로알려진미국의경우다른나라에비해발견되는대립유전자의수가상대적으로많다 [11]. 한국인은비교적 HLA 다형성이높지않은것으로알려져있

5 Lee KW, et al., New HLA Nomenclature (2010) 207 Table 3. HLA-A alleles identified in Koreans A*01:01 A*0101 A1 A*24:13 A*2413 A24 (9) A*01:02 A*0102 A1 A*24:20 A*2420 A24 (9) A*02:01 A*0201 A2 A*24:21 A*2421 A24 (9) A*02:02 A*0202 A2 A*24:28 A*2428 A24 (9) A*02:03 A*0203 A203 A*24:30 A* A*02:05 A*0205 A2 A*24:37 A*2437 A24 (9) A*02:06 A*0206 A2 A*24:50 A* A*02:07 A*0207 A2 A*24:74 A* A*02:10 A*0210 A210 A*24:75 A* A*02:12 A*0212 A2 A*25:01 A*2501 A25 (10) A*02:15N A*0215N Null A*26:01 A*2601 A26 (10) A*02:28 A* A*26:02 A*2602 A26 (10) A*02:36 A* A*26:03 A*2603 A26 (10) A*02:41 A*0241 A2 A*26:10 A*2610 A10 A*02:53N A*0253N Null A*26:14 A* A*02:55 A* A*26:18 A* A*02:61 A* A*26:20 A* A*02:76 A* A*26:32 A* A*02:86 A* A*26:34 A* A*02:87 A* A*26:36 A* A*02:90 A*0290 A2 A*29:01 A*2901 A29 (19) A*02:91 A* A*30:01 A*3001 A30 (19) A*03:01 A*0301 A3 A*30:02 A*3002 A30 (19) A*03:02 A*0302 A3 A*30:04 A*3004 A30 (19) A*03:19 A* A*31:01 A*3101 A31 (19) A*11:01 A*1101 A11 A*31:02 A*3102 A31 (19) A*11:02 A*1102 A11 A*31:05 A*3105 A31 (19) A*11:04 A*1104 A11 A*31:11 A* A*11:07 A*1107 A11 A*32:01 A*3201 A32 (19) A*11:20 A* A*32:08 A* A*11:35 A* A*33:03 A*3303 A33 (19) A*23:01 A*2301 A23 (9) A*33:08 A*3308 A33 (19) A*24:02 A*2402 A24 (9) A*33:10 A* A*24:03 A*2403 A2403 A*33:14 A* A*24:04 A*2404 A24 (9) A*33:15 A* A*24:05 A*2405 A24 (9) A*68:01 A*6801 A68 (28) A*24:07 A*2407 A24 (9) A*68:24 A* A*24:08 A*2408 A24 (9) A*68:38 A* A*24:10 A*2410 A2403 A*69:01 A*6901 A69 (28) Published [12, 13] and unpublished alleles (up to the 2nd field in the nomenclature) recognized by authors as of 31st March 2010 are listed. Alleles with frequencies of 0.5% are bolded with underline. Alleles with frequencies of % are underlined. Others are either very rare (<0.1%) or recently characterized. 으나최근에다문화가정의비율이증가되고있어앞으로국내에서발견되는 HLA 대립유전자의수는점차늘어갈것으로예측된다. 본종설에서는최근까지 (2010년 3월까지 ) 보고되었거나 [12-15] 국내 HLA 전문가들로부터입수한미발표자료를토대로, 한국인에서발견된적이있는모든 HLA-A, -B, -C, -DRB1, -DQB1 대립유전자들을집계하였다. 이들에대한신규명명 (2010) 과이전의명명, 그리고관련혈청학적특이성등을 Table 3-7에나열하였다. 대립유전자명칭은위에기술한 1-2영역만을표시하였다 ( 예. A*01:01). 이중에는극히드문대립유전자들도많이포함되어 있으므로한국인에서발견된대립유전자의빈도를대략적으로파악할수있도록 3가지 ( 0.5%, %, <0.1%) 로구분하여표시하였다. 현재까지한국인에서발견된 null 대립유전자로는 A*02:15N과 A*2:53N이있다 (Table 3). 또한가지특기할점은한국인에존재하는것으로알려진기존의 DRB1*14:01 대립유전자가모두 DRB1*14:54 (Table 6) 로최근에밝혀졌다 [15]. DRB1*14:54는 DRB1*14:01:01과 codon 112번 (exon 3) 에아미노산차이 (His>Tyr) 를유도하는 1개의염기서열차이 (CAC> TAC) 를나타낸다.

6 208 Korean J Lab Med 2010;30: Table 4. HLA-B alleles identified in Koreans B*07:02 B*0702 B7 B*39:10 B*3910 B39 (16) B*07:05 B*0705 B7 B*40:01 B*4001 B60 (40) B*07:31 B* B*40:02 B*4002 B61 (40) B*07:43 B* B*40:03 B*4003 B61 (40) B*08:01 B*0801 B8 B*40:06 B*4006 B61 (40) B*13:01 B*1301 B13 B*40:21 B* B*13:02 B*1302 B13 B*40:26 B*4026 B21 B*14:01 B*1401 B64 (14) B*40:40 B* B*14:02 B*1402 B65 (14) B*40:49 B* B*15:01 B*1501 B62 (15) B*40:62 B* B*15:02 B*1502 B75 (15) B*40:71 B* B*15:03 B*1503 B72 (70) B*40:73 B* B*15:07 B*1507 B62 (15) B*40:83 B* B*15:08 B*1508 B75 (15) B*40:85 B* B*15:10 B*1510 B71 (70) B*41:01 B*4101 B41 B*15:11 B*1511 B75 (15) B*42:01 B*4201 B42 B*15:12 B*1512 B76 (15) B*44:02 B*4402 B44 (12) B*15:14 B*1514 B76 (15) B*44:03 B*4403 B44 (12) B*15:17 B*1517 B63 (15) B*45:01 B*4501 B45 (12) B*15:18 B*1518 B71 (70) B*46:01 B*4601 B46 B*15:25 B*1525 B62 (15) B*46:17 B* B*15:27 B*1527 B62 (15) B*47:01 B*4701 B47 B*15:28 B*1528 B62 (15) B*48:01 B*4801 B48 B*15:29 B*1529 B15 B*48:11 B* B*15:30 B*1530 B62 (15) B*49:01 B*4901 B49 (21) B*15:32 B*1532 B62 (15) B*50:01 B*5001 B50 (21) B*15:35 B*1535 B62 (15) B*51:01 B*5101 B51 (5) B*15:38 B* B*51:02 B*5102 B5102 B*15:58 B*1558 B62 (15) B*51:06 B*5106 B51 (5) B*15:68 B*1568 B35 B*51:24 B*5124 B51 (5) B*15:78 B*1578 B15 B*51:37 B* B*15:85 B* B*51:58 B* B*15:87 B* B*52:01 B*5201 B52 (5) B*18:01 B*1801 B18 B*52:06 B*5206 B52 (5) B*27:04 B*2704 B27 B*54:01 B*5401 B54 (22) B*27:05 B*2705 B27 B*54:19 B* B*27:07 B*2707 B27 B*55:01 B*5501 B55 (22) B*27:20 B*2720 B27 B*55:02 B*5502 B55 (22) B*35:01 B*3501 B35 B*55:04 B*5504 B55 (22) B*35:02 B*3502 B35 B*55:07 B*5507 B54 (22) B*35:03 B*3503 B35 B*55:13 B* B*35:05 B*3505 B35 B*55:19 B* B*35:08 B*3508 B35 B*56:01 B*5601 B56 (22) B*35:11 B*3511 B35 B*56:03 B*5603 B22 B*35:31 B* B*56:04 B*5604 B56 (22) B*35:63 B* B*56:05 B*5605 B56 (22) B*35:64 B* B*57:01 B*5701 B57 (17) B*37:01 B*3701 B37 B*57:02 B*5702 B57 (17) B*37:05 B* B*58:01 B*5801 B58 (17) B*38:01 B*3801 B38 (16) B*58:02 B* B*38:02 B*3802 B38 (16) B*58:13 B* B*39:01 B*3901 B3901 B*59:01 B*5901 B59 B*39:02 B*3902 B3902 B*67:01 B*6701 B67 B*39:04 B*3904 B39 (16) B*81:01 B*8101 B81 B*39:05 B*3905 B39 (16) Published [12, 13] and unpublished alleles (up to the 2nd field in the nomenclature) recognized by authors as of 31st March 2010 are listed. Alleles with frequencies of 0.5% are bolded with underline. Alleles with frequencies of % are underlined. Others are either very rare (<0.1%) or recently characterized.

7 Lee KW, et al., New HLA Nomenclature (2010) 209 새로운 HLA 명명법 (2010) 과이전명명법의주요차이점 1. 각영역의구분을위한콜론 ( : ) 삽입 이제까지사용해온명명법은 2004년에개정된것이며 [16], 이전의명명을새로운명명으로전환한예는 Fig. 2A와같다. 이전의명명에서는각영역에구분표시가없이두자릿수씩할당되어 4-8자릿수로구성되어있었기때문에각각의영역에서 99개까지만명명을할수있다는한계점이있었다. 이때문에대립유전자의수가 99개를초과했던 A*02와 B*15군의경우, 명명에사용하지않고있던숫자 92 와 95 를각각이용하여 A*02 와 B*15군의초과대립유전자들을명명해왔었다 (rollover)[17]. 또한, DPB1 대립유전자의명명에서도 DPB1*9901 다음에발견된대립유전자는 DPB1*0102, DPB1*0203, DPB1*0302 등으로염기서열유사성과상관없이밀려서명명이되어왔다. 위에서설명한바와같이개정된명명에서는콜론 (:) 삽입으로영역간경계표시를하였기때문에영역안에포함하는자릿수에제한이없어지게되었다. 2. HLA-A*92군, -B*95군, -DPB1 대립유전자명명의변화콜론 (:) 삽입으로영역간의경계표시가가능해짐에따라, 99 개를초과하는대립유전자의명명도가능해져그간의문제가 Table 5. HLA-C alleles identified in Koreans C*01:02 C*0102 Cw1 C*06:12 C* C*01:03 C*0103 Cw1 C*07:01 C*0701 Cw7 C*01:11 C* C*07:02 C*0702 Cw7 C*02:02 C*0202 Cw2 C*07:04 C*0704 Cw7 C*03:02 C*0302 Cw10 (w3) C*07:06 C*0706 Cw7 C*03:03 C*0303 Cw9 (w3) C*08:01 C*0801 Cw8 C*03:04 C*0304 Cw10 (w3) C*08:02 C*0802 Cw8 C*03:38 C* C*08:03 C*0803 Cw8 C*03:46 C*0346 Cw10 (w3) C*08:06 C* C*03:49 C* C*12:02 C* C*04:01 C*0401 Cw4 C*12:03 C* C*04:03 C* C*14:02 C* C*04:36 C* C*14:03 C* C*05:01 C*0501 Cw5 C*15:02 C* C*06:02 C*0602 Cw6 C*15:05 C* Published [12] and unpublished alleles (up to the 2nd field in the nomenclature) recognized by authors as of 31st March 2010 are listed. Alleles with frequencies of 0.5% are bolded with underline. Alleles with frequencies of % are underlined. Others are either very rare (<0.1%) or recently characterized. A* A*01:01:01:01 A* A*33:03:01 B* L B*39:01:01:02L B*1507 B*15:07 DRB1* DRB1*07:01:01:01 DRB1*1454 DRB1*14:54 DQB1* DQB1*06:02:01 DQB1*0626N DQB1*06:26N...etc A A*9201 A*02:101 A*9202 A*02:102 A*9203 A*02:103...etc B*9501 B*15:101 B*9502 B*15:102 B*9503 B*15:103...etc B DPB1*0102 DPB1*100:01 DPB1*0203 DPB1*101:01 DPB1*0302 DPB1*102:01 DPB1*0403 DPB1*103:01...etc C Cw*0103 C*01:03 Cw* C*02:02:01 Cw*0322Q C*03:22Q Cw* C*07:02:01:01...etc D Fig. 2. Example of names converted from old to new version of the nomenclature. (A) General examples of name conversion for HLA-A, -B, -DRB1, and -DQB1 alleles. (B) Examples of name conversion for A*92 and B*95 allele families. (C) Examples of name conversion for DPB1 alleles. (D) Examples of name conversion for C alleles.

8 210 Korean J Lab Med 2010;30: Table 6. HLA-DRB1 alleles identified in Koreans DRB1*01:01 DRB1*0101 DR1 DRB1*11:06 DRB1*1106 DR11 (5) DRB1*01:02 DRB1*0102 DR1 DRB1*11:08 DRB1*1108 DR11 (5) DRB1*03:01 DRB1*0301 DR17 (3) DRB1*11:11 DRB1*1111 DR11 (5) DRB1*03:04 DRB1*0304 DR17 (3) DRB1*12:01 DRB1*1201 DR12 (5) DRB1*04:01 DRB1*0401 DR4 DRB1*12:02 DRB1*1202 DR12 (5) DRB1*04:02 DRB1*0402 DR4 DRB1*12:05 DRB1*1205 DR12 (5) DRB1*04:03 DRB1*0403 DR4 DRB1*12:06 DRB1*1206 DR12 (5) DRB1*04:04 DRB1*0404 DR4 DRB1*12:07 DRB1* DRB1*04:05 DRB1*0405 DR4 DRB1*12:08 DRB1* DRB1*04:06 DRB1*0406 DR4 DRB1*12:10 DRB1* DRB1*04:07 DRB1*0407 DR4 DRB1*12:13 DRB1* DRB1*04:08 DRB1*0408 DR4 DRB1*12:17 DRB1* DRB1*04:10 DRB1*0410 DR4 DRB1*13:01 DRB1*1301 DR13 (6) DRB1*04:22 DRB1*0422 DR4 DRB1*13:02 DRB1*1302 DR13 (6) DRB1*04:45 DRB1* DRB1*13:06 DRB1*1306 DR13 (6) DRB1*04:51 DRB1* DRB1*13:07 DRB1*1307 DR13 (6) DRB1*04:68 DRB1* DRB1*13:10 DRB1*1310 DR13 (6) DRB1*07:01 DRB1*0701 DR7 DRB1*13:12 DRB1*1312 DR13 (6) DRB1*07:04 DRB1*0704 DR7 DRB1*13:39 DRB1* DRB1*07:05 DRB1* DRB1*14:02 DRB1*1402 DR14 (6) DRB1*08:01 DRB1*0801 DR8 DRB1*14:03 DRB1*1403 DR1403 DRB1*08:02 DRB1*0802 DR8 DRB1*14:04 DRB1*1404 DR1404 DRB1*08:03 DRB1*0803 DR8 DRB1*14:05 DRB1*1405 DR14 (6) DRB1*08:04 DRB1*0804 DR8 DRB1*14:06 DRB1*1406 DR14 (6) DRB1*08:06 DRB1*0806 DR8 DRB1*14:07 DRB1*1407 DR14 (6) DRB1*08:09 DRB1*0809 DR8 DRB1*14:10 DRB1*1410 DR14 (6) DRB1*08:13 DRB1* DRB1*14:12 DRB1*1412 DR14 (6) DRB1*08:29 DRB1* DRB1*14:44 DRB1* DRB1*09:01 DRB1*0901 DR9 DRB1*14:54 DRB1* DRB1*09:04 DRB1* DRB1*14:56 DRB1* DRB1*09:08 DRB1* DRB1*14:78 DRB1* DRB1*10:01 DRB1*1001 DR10 DRB1*15:01 DRB1*1501 DR15 (2) DRB1*11:01 DRB1*1101 DR11 (5) DRB1*15:02 DRB1*1502 DR15 (2) DRB1*11:02 DRB1*1102 DR11 (5) DRB1*15:03 DRB1*1503 DR15 (2) DRB1*11:03 DRB1*1103 DR11 (5) DRB1*15:04 DRB1*1504 DR15 (2) DRB1*11:04 DRB1*1104 DR11 (5) DRB1*16:02 DRB1*1602 DR16 (2) Published [12-15] and unpublished alleles (up to the 2nd field in the nomenclature) recognized by authors as of 31st March 2010 are listed. Alleles with frequencies of 0.5% are bolded with underline. Alleles with frequencies of % are underlined. Others are either very rare (<0.1%) or recently characterized. Recent study has revealed that previously assigned DRB1*14:01 in Koreans were actually DRB1*14:54 [15]. 모두해결되었다. 즉, 두군 (A*92, B*95) 의대립유전자는원래의 A*02와 B*15 대립유전자군시리즈로다시복귀시켜 Fig. 2B ( 예. A*9201 A*02:101; B*9501 B*15:101) 와같이명명을전환하였으며, DPB1*9901 이후에명명된 DPB1 대립유전자들은 Fig. 2C ( 예. DPB1*0102 DPB1*100:01) 와같이재명명되었다. Fig. 2B에나타난바와같이, A*02와 B*15군으로의명명전환에서자연스러운전환을위해공백으로남는 A*02:100과 B*15:100의명명은앞으로도부여되지않을것이다. DPB1*100 이후의명칭을갖는 DPB1 대립유전자의경우, 신 / 구명명의상호연관성이매우떨어지기때문에 명명전환표 를이용하는것이큰도움이될것이다 (Table 8). 3. HLA-C 대립유전자명명의변화 HLA-C 대립유전자명명에서는앞으로 w 표기를삭제하기로했다 (Fig. 2D). 그러나보체계인자 (complement factor) 들과의혼란을피하고또 KIR (killer-cell immunoglobulinlike receptor) 에대한리간드 (ligand) 로작용하는 HLA-C 분자의항원요소 (epitope) 를 C1 혹은 C2 라는용어로종종표기하므로혼선을막기위해 HLA-C의혈청학적형별에대한명명에서는 w 표기를계속유지하기로하였다 ( 예. Cw1, Cw2, Cw3 등 ). 전체대립유전자에대한새로운명명과이전명명의대조표는 WHO HLA 명명위원회의 2010년도보고서에포함되어있으며 [5], 새명명으로전환해줄수있는전환프로그램이

9 Lee KW, et al., New HLA Nomenclature (2010) 211 Table 7. HLA-DQB1 alleles identified in Koreans 2010 designation Published [12] and unpublished alleles (up to the 2nd field in the nomenclature) recognized by authors as of 31st March 2010 are listed. Alleles with frequencies of 0.5% are bolded with underline. Others are either very rare (<0.1%) or recently characterized. IMGT/HLA 데이터베이스웹사이트 ( 에도제공되고있다. 4. P 와 G 접미사의도입 Pre-2010 designation HLA specificity DQB1*02:01 DQB1*0201 DQ2 DQB1*02:02 DQB1*0202 DQ2 DQB1*03:01 DQB1*0301 DQ7 (3) DQB1*03:02 DQB1*0302 DQ8 (3) DQB1*03:03 DQB1*0303 DQ9 (3) DQB1*03:14 DQB1* DQB1*04:01 DQB1*0401 DQ4 DQB1*04:02 DQB1*0402 DQ4 DQB1*05:01 DQB1*0501 DQ5 (1) DQB1*05:02 DQB1*0502 DQ5 (1) DQB1*05:03 DQB1*0503 DQ5 (1) DQB1*06:01 DQB1*0601 DQ6 (1) DQB1*06:02 DQB1*0602 DQ6 (1) DQB1*06:03 DQB1*0603 DQ6 (1) DQB1*06:04 DQB1*0604 DQ6 (1) DQB1*06:09 DQB1*0609 DQ6 (1) 새로운 HLA 명명법의또다른특징은, 접미사 P 와 G 의도입이다. HLA 분자의다형성은펩티드결합부위에집중되어있기때문에, 그에해당되는 HLA 유전자부위 (HLA class I 대립유전자의 exon 2-3, HLA class II 대립유전자의 exon 2) 의염기서열차이를구별할수있도록 HLA DNA 형별분석법이개발되어왔다. 그러나, 새로운대립유전자의염기서열이끊임없이발견됨에따라펩티드결합부위외의부위에도상대적으로규모는작지만염기다양성이존재하고있다는사실이밝혀지게되었다. 따라서펩티드결합부위를중심으로실시해온이제까지의분석방법으로는추가검사를실시하지않는한정확한대립유전자분석을할수없게되었으며분석결과로도출된모든대립유전자를 검사결과지 에기록해야하는상황이빈번히초래되고있다. 예를들면, A*24:02:01:01/24:02:01:02L/24: 02:03/24:02:10/24:02:13/24:02:31/24:09N/24:11N/24:40N/ 24:76/24:79/24:83N으로표기하던지, DRB1*14:01:01/14:54 로표기하고있다. 이에따라, 이들애매한대립유전자들 (ambiguous string of alleles) 을집합체로단순화시켜표기하는 Table 8. DPB1 alleles showing drastic changes in Nomenclature DPB1*100:01 DPB1*101:01 DPB1*102:01 DPB1*103:01 DPB1*104:01 DPB1*105:01 DPB1*106:01 DPB1*107:01 DPB1*108:01 DPB1*109:01 DPB1*110:01 DPB1*111:01 DPB1*112:01 DPB1*113:01 DPB1*114:01 DPB1*115:01 DPB1*116:01 DPB1*117:01 DPB1*118:01 DPB1*119:01 DPB1*120:01N DPB1*121:01 DPB1*122:01 DPB1*123:01 DPB1*124:01 DPB1*125:01 Selected from the reference [5]. DPB1*0102 DPB1*0203 DPB1*0302 DPB1*0403 DPB1*0502 DPB1*0602 DPB1*0802 DPB1*0902 DPB1*1002 DPB1*1102 DPB1*1302 DPB1*1402 DPB1*1502 DPB1*1602 DPB1*1702 DPB1*1802 DPB1*1902 DPB1*2002 DPB1*2102 DPB1*2202 DPB1*2302N DPB1*2402 DPB1*2502 DPB1*2602 DPB1*2702 DPB1*2802 것이임상에서번거로움을피할수있으며이를위해새롭게접미사 P 와 G 의개념을도입하게되었다. 접미사 P 는펩티드결합부위의아미노산서열이동일한 HLA 대립유전자의집합체를의미하는것으로, 각대립유전자군에서최소숫자대립유전자명칭의두번째영역끝에대문자 P를붙인다 (Table 9). 예를들어, A*02:01P는펩티드결합부위의아미노산서열이 A*02:01:01:01과동일한대립유전자들의집합체를의미하며 54개의대립유전자들이포함된다. 따라서, P군에포함되는대부분의대립유전자는 1-2 영역의숫자는동일하고 3-4 영역의숫자가다른것들이며, 발현되지않는 null 대립유전자는포함되지않는다. P군에포함되는대립유전자의일부는 2영역의숫자가다른것들도있는데, 이들은펩티드결합부위의아미노산서열은동일하지만그외부위의아미노산서열이다른것들이다 ( 예. A*01:01P군의 A*01:32, A*01:37, A*01:45). Table 9에는한국인에서발견되는 HLA-A, -B, -C, -DRB1, -DQB1 대립유전자들을중심으로 P 군을선정하여나열하고, 해당 P 군에속하는현재까지알려진모든대립유전자를나열하였다.

10 212 Korean J Lab Med 2010;30: Table 9. HLA P groups selected for Koreans Group designation N of alleles in group Alleles within group A*01:01P 17 A*01:01:01:01/01:01:02/01:01:03/01:01:04/01:01:05/01:01:06/01:01:07/01:01:08/01:01:09/01:01:10/01:01:11/01:01:12/ 01:01:13/01:01:14/01:32/01:37/01:45 A*02:01P 54 A*02:01:01:01/02:01:01:02L/02:01:01:03/02:01:02/02:01:03/02:01:04/02:01:05/02:01:06/02:01:07/02:01:08/02:01:09/ 02:01:10/02:01:11/02:01:12/02:01:13/02:01:14/02:01:15/02:01:17/02:01:18/02:01:19/02:01:21/02:01:22/02:01:23/ 02:01:24/02:01:25/02:01:26/02:01:27/02:01:28/02:01:29/02:01:30/02:01:31/02:01:32/02:01:33/02:01:34/02:01:35/ 02:01:36/02:01:37/02:01:38/02:01:39/02:01:40/02:01:41/02:01:42/02:01:43/02:01:44/02:01:45/02:09/02:66/02:75/ 02:89/02:97:01/02:97:02/02:132/02:134/02:140 A*02:03P 2 A*02:03:01/02:03:02 A*02:05P 4 A*02:05:01/02:05:02/02:05:03/02:179 A*02:06P 10 A*02:06:01/02:06:02/02:06:03/02:06:04/02:06:05/02:06:06/02:06:07/02:06:08/02:06:09/02:126 A*03:01P 22 A*03:01:01:01/03:01:01:03/03:01:02/03:01:03/03:01:04/03:01:05/03:01:06/03:01:07/03:01:08/03:01:09/03:01:10/03:01:11/ 03:01:12/03:01:13/03:01:14/03:01:15/03:01:16/03:01:17/03:20/03:26/03:37/03:45 A*11:01P 17 A*11:01:01/11:01:02/11:01:03/11:01:04/11:01:05/11:01:06/11:01:07/11:01:08/11:01:09/11:01:10/11:01:11/11:01:12/ 11:01:13/11:01:14/11:01:15/11:01:16/11:01:17 A*11:02P 4 A*11:02:01/11:02:02/11:02:03/11:53 A*23:01P 6 A*23:01:01/23:01:02/23:17/23:18/23:19Q/23:20 A*24:02P 34 A*24:02:01:01/24:02:01:02L/24:02:02/4:02:03/24:02:04/24:02:05/24:02:06/24:02:07/24:02:08/24:02:09/24:02:10/ 24:02:11/24:02:12/24:02:13/24:02:14/24:02:15/24:02:16/24:02:17/24:02:18/24:02:19/24:02:20/24:02:21/24:02:22/ 24:02:23/24:02:24/24:02:25/24:02:26/24:02:27/24:02:28/24:02:29/24:02:30/24:02:31/24:76/24:79 A*24:03P 3 A*24:03:01/24:03:02/24:33 A*24:13P 2 A*24:13:01/24:13:02 A*25:01P 3 A*25:01:01/25:01:02/25:07 A*26:01P 15 A*26:01:01/26:01:02/26:01:03/26:01:04/26:01:05/26:01:06/26:01:07/26:01:08/26:01:09/26:01:10/26:01:11/26:01:12/ 26:01:13/26:24/26:26 A*26:03P 2 A*26:03:01/26:03:02 A*29:01P 2 A*29:01:01:01/29:01:02 A*30:01P 4 A*30:01:01/30:01:02/30:01:03/30:24 A*30:02P 6 A*30:02:01/30:02:02/30:02:03/30:02:04/30:02:05/30:33 A*31:01P 7 A*31:01:02/31:01:03/31:01:04/31:01:05/31:01:06/31:01:07/31:23 A*32:01P 5 A*32:01:01/32:01:02/32:01:03/32:01:04/32:01:05 A*33:03P 7 A*33:03:01/33:03:02/33:03:03/33:03:04/33:03:05/33:15/33:25 A*68:01P 8 A*68:01:01/68:01:02/68:01:03/68:01:04/68:01:05/68:01:06/68:01:07/68:33 B*07:02P 23 B*07:02:01/07:02:02/07:02:03/07:02:04/07:02:05/07:02:06/07:02:07/07:02:08/07:02:09/07:02:10/07:02:11/07:02:12/ 07:02:13/07:02:14/07:02:15/07:02:16/07:02:17/07:02:18/07:02:19/07:44/07:58/07:59/07:61 B*07:05P 5 B*07:05:01/07:05:02/07:05:03/07:05:04/07:06 B*08:01P 10 B*08:01:01/08:01:02/08:01:03/08:01:04/08:01:05/08:01:06/08:01:07/08:01:08/08:01:09/08:01:10 B*13:01P 3 B*13:01:01/13:01:02/13:01:03 B*13:02P 7 B*13:02:01/13:02:02/13:02:03/13:02:04/13:02:05/13:02:06/13:02:07 B*14:02P 5 B*14:02:01/14:02:02/14:02:03/14:02:04/14:02:05 B*15:01P 19 B*15:01:01:01/15:01:02/15:01:03/15:01:04/15:01:06/15:01:07/15:01:08/15:01:09/15:01:10/15:01:11/15:01:12/15:01:13/ 15:01:14/15:01:15/15:01:16/15:102/15:104/5:140/15:146 B*15:02P 4 B*15:02:01/15:02:02/15:02:03/15:02:04 B*15:03P 4 B*15:03:01/15:03:02/15:03:03/15:103 B*15:10P 2 B*15:10:01/15:10:02 B*15:11P 4 B*15:11:01/15:11:02/15:11:03/15:11:04 B*15:12P 2 B*15:12/15:19 B*15:17P 3 B*15:17:01:01/15:17:01:02/15:17:02 B*15:18P 4 B*15:18:01/15:18:02/15:18:03/15:18:04 B*15:25P 2 B*15:25:01/15:25:02 B*15:27P 3 B*15:27:01/15:27:02/15:27:03 B*15:38P 2 B*15:38:01/15:38:02 B*15:78P 2 B*15:78:01/15:78:02 B*18:01P 8 B*18:01:01/18:01:02/18:01:03/18:01:04/18:01:05/18:01:06/18:01:07/18:01:08 B*27:04P 3 B*27:04:01/27:04:02/27:04:03 B*27:05P 13 B*27:05:02/27:05:03/27:05:04/27:05:05/27:05:06/27:05:07/27:05:08/27:05:09/27:05:10/27:05:11/27:05:12/27:05:13/27:13 B*35:01P 23 B*35:01:01/35:01:02/35:01:03/35:01:04/35:01:05/35:01:06/35:01:07/35:01:08/35:01:09/35:01:10/35:01:11/35:01:12/ 35:01:13/35:01:14/35:01:15/35:01:16/35:01:17/35:01:18/35:01:19/35:42:01/35:42:02/35:57/35:94 B*35:02P 4 B*35:02:01/35:02:02/35:02:03/35:02:04 (Continued to the next page)

11 Lee KW, et al., New HLA Nomenclature (2010) 213 Table 9. (Continued from the previous page) HLA P groups selected for Koreans Group designation N of alleles in group Alleles within group B*35:03P 5 B*35:03:01/35:03:02/35:03:03/35:03:04/35:70 B*35:05P 2 B*35:05:01/35:05:02 B*35:08P 4 B*35:08:01/35:08:02/35:08:03/35:08:04 B*37:01P 7 B*37:01:01/37:01:02/37:01:03/37:01:04/37:01:05/37:01:06/37:01:07 B*38:01P 4 B*38:01:01/38:01:02/38:01:03/38:01:04 B*38:02P 3 B*38:02:01/38:02:02/38:18 B*39:01P 12 B*39:01:01:01/39:01:01:02L/39:01:03/39:01:04/39:01:05/39:01:06/39:01:07/39:01:08/39:01:09/39:01:10/39:01:11/39:46 B*39:02P 2 B*39:02:01/39:02:02 B*39:05P 2 B*39:05:01/39:05:02 B*40:01P 11 B*40:01:01/40:01:02/40:01:03/40:01:04/40:01:05/40:01:06/40:01:07/40:01:08/40:01:09/40:01:10/40:55 B*40:02P 12 B*40:02:01/40:02:02/40:02:03/40:02:04/40:02:05/40:02:06/40:02:07/40:02:08/40:02:09/40:02:10/40:56/40:97 B*40:06P 3 B*40:06:01:01/40:06:01:02/40:06:02 B*42:01P 2 B*42:01:01/42:01:02 B*44:02P 16 B*44:02:01:01/44:02:01:02S/44:02:02/44:02:03/44:02:04/44:02:05/44:02:06/44:02:07/44:02:08/44:02:09/44:02:10/ 44:02:11/44:02:12/44:02:13/44:27/44:66 B*44:03P 11 B*44:03:01/44:03:02/44:03:03/44:03:04/44:03:05/44:03:06/44:03:07/44:03:08/44:03:09/44:03:10/44:03:11 B*45:01P 2 B*45:01/45:07 B*46:01P 4 B*46:01:01/46:01:02/46:01:03/46:01:04 B*47:01P 2 B*47:01:01:01/47:01:01:02 B*48:01P 3 B*48:01:01/48:01:02/48:09 B*49:01P 2 B*49:01:01/49:01:02 B*50:01P 2 B*50:01:01/50:01:02 B*51:01P 21 B*51:01:01/51:01:02/51:01:03/51:01:04/51:01:05/51:01:06/51:01:07/51:01:08/51:01:09/51:01:10/51:01:11/51:01:12/ 51:01:13/51:01:14/51:01:15/51:01:16/51:01:17/51:30/51:32/51:48/51:51 B*51:02P 4 B*51:02:01/51:02:02/51:02:03/51:02:04 B*51:24P 3 B*51:24:01/51:24:02/51:24:03 B*52:01P 6 B*52:01:01/52:01:02/52:01:03/52:01:04/52:01:05/52:07 B*52:06P 2 B*52:06:01/52:06:02 B*54:01P 2 B*54:01/54:17 B*55:01P 6 B*55:01:01/55:01:02/55:01:03/55:01:04/55:01:05/55:01:06 B*55:02P 5 B*55:02:01/55:02:02/55:02:03/55:02:04/55:02:05 B*56:01P 5 B*56:01:01/56:01:02/56:01:03/56:01:04/56:24 B*56:05P 2 B*56:05:01/56:05:02 B*57:01P 8 B*57:01:01/57:01:02/57:01:03/57:01:04/57:01:05/57:01:06/57:01:07/57:29 B*57:02P 2 B*57:02:01/57:02:02 B*58:01P 5 B*58:01:01/58:01:02/58:01:03/58:01:04/58:11 B*67:01P 2 B*67:01:01/67:01:02 B*81:01P 3 B*81:01/81:02/81:03 C*01:02P 11 C*01:02:01/01:02:02/01:02:03/01:02:04/01:02:05/01:02:06/01:02:07/01:02:08/01:02:09/01:11/01:25 C*01:03P 2 C*01:03/01:24 C*02:02P 12 C*02:02:01/02:02:02/02:02:03/02:02:05/02:02:06/02:02:07/02:02:08/02:02:09/02:02:10/02:02:11/02:10/02:29 C*03:02P 6 C*03:02:01/03:02:02/03:02:03/03:02:04/03:02:05/03:02:06 C*03:03P 12 C*03:03:01/03:03:02/03:03:03/03:03:04/03:03:05/03:03:06/03:03:07/03:03:08/03:03:09/03:03:10/03:03:11/03:62 C*03:04P 20 C*03:04:01:01/03:04:01:02/03:04:02/03:04:03/03:04:04/03:04:05/03:04:06/03:04:07/03:04:08/03:04:09/03:04:10/03:04:11/ 03:04:12/03:04:13/03:04:14/03:04:15/03:04:16/03:04:17/03:04:18/03:04:19 C*03:38P 2 C*03:38:01/03:38:02 C*04:01P 21 C*04:01:01:01/04:01:01:02/04:01:01:03/04:01:02/04:01:03/04:01:04/04:01:05/04:01:06/04:01:07/04:01:08/04:01:09/ 04:01:10/04:01:11/04:01:12/04:01:13/04:01:14/04:01:15/04:01:16/04:28/04:30/04:41 C*05:01P 16 C*05:01:01:01/05:01:01:02/05:01:02/05:01:03/05:01:04/05:01:05/05:01:06/05:01:07/05:01:08/05:01:09/05:01:10/05:01:11/ 05:01:12/05:01:13/05:03/05:37 C*06:02P 6 C*06:02:01:01/06:02:01:02/06:02:03/06:02:04/06:02:05/06:17 C*07:01P 15 C*07:01:01/07:01:02/07:01:03/07:01:04/07:01:05/07:01:06/07:01:07/07:01:08/07:01:09/07:01:10/07:01:11/07:01:12/ 07:06/07:18/07:52 C*07:02P 19 C*07:02:01:01/07:02:01:02/07:02:01:03/07:02:02/07:02:03/07:02:04/07:02:05/07:02:06/07:02:07/07:02:08/07:02:09/ 07:02:10/07:02:11/07:02:12/07:02:13/07:02:14/07:50/07:66/07:74 C*07:04P 4 C*07:04:01/07:04:02/07:04:03/07:11 C*08:01P 5 C*08:01:01/08:01:02/08:20/08:22/08:24 C*08:02P 3 C*08:02:01/08:02:02/08:02:03 (Continued to the next page)

12 214 Korean J Lab Med 2010;30: Table 9. (Continued from the previous page) HLA P groups selected for Koreans Group designation N of alleles in group Alleles within group C*08:03P 2 C*08:03:01/08:03:02 C*12:02P 5 C*12:02:01/12:02:02/12:02:03/12:02:04/12:02:05 C*12:03P 13 C*12:03:01:01/12:03:01:02/12:03:02/12:03:03/12:03:04/12:03:05/12:03:06/12:03:07/12:03:08/12:03:09/12:03:10/12:03:11/ 12:23 C*14:02P 5 C*14:02:01/14:02:02/14:02:03/14:02:04/14:11 C*15:02P 6 C*15:02:01/15:02:02/15:02:03/15:02:04/15:02:05/15:13 C*15:05P 4 C*15:05:01/15:05:02/15:05:03/15:05:04 DRB1*01:01P 18 DRB1*01:01:01/01:01:02/01:01:03/01:01:04/01:01:05/01:01:06/01:01:07/01:01:08/01:01:09/01:01:10/01:01:11/01:01:12/ 01:01:13/01:01:14/01:01:15/01:01:16/01:01:17/01:01:18 DRB1*01:02P 5 DRB1*01:02:01/01:02:02/01:02:03/01:02:04/01:02:05 DRB1*03:01P 10 DRB1*03:01:01:01/03:01:01:02/03:01:02/03:01:03/03:01:04/03:01:05/03:01:06/03:01:07/03:01:08/03:01:09 DRB1*04:01P 6 DRB1*04:01:01/04:01:02/04:01:03/04:01:04/04:01:05/04:01:06 DRB1*04:03P 5 DRB1*04:03:01/04:03:02/04:03:03/04:03:04/04:03:05 DRB1*04:04P 5 DRB1*04:04:01/04:04:02/04:04:03/04:04:04/04:04:05 DRB1*04:05P 10 DRB1*04:05:01/04:05:02/04:05:03/04:05:04/04:05:05/04:05:06/04:05:07/04:05:08/04:05:09/04:05:10 DRB1*04:06P 3 DRB1*04:06:01/04:06:02/04:06:03 DRB1*04:07P 4 DRB1*04:07:01/04:07:02/04:07:03/04:07:04 DRB1*04:08P 2 DRB1*04:08:01/04:08:02 DRB1*07:01P 4 DRB1*07:01:01:01/07:01:01:02/07:01:02/07:01:03 DRB1*08:01P 5 DRB1*08:01:01/08:01:02/08:01:03/08:01:04/08:01:05 DRB1*08:02P 3 DRB1*08:02:01/08:02:02/08:02:03 DRB1*08:04P 5 DRB1*08:04:01/08:04:02/08:04:03/08:04:04/08:04:05 DRB1*09:01P 6 DRB1*09:01:02/09:01:03/09:01:04/09:01:05/09:01:06/09:01:07 DRB1*10:01P 3 DRB1*10:01:01/10:01:02/10:01:03 DRB1*11:01P 11 DRB1*11:01:01/11:01:02/11:01:03/11:01:04/11:01:05/11:01:06/11:01:07/11:01:08/11:01:09/11:01:10/11:01:11 DRB1*11:02P 2 DRB1*11:02:01/11:02:02 DRB1*11:04P 5 DRB1*11:04:01/11:04:02/11:04:03/11:04:04/11:04:05 DRB1*11:06P 2 DRB1*11:06:01/11:06:02 DRB1*11:08P 2 DRB1*11:08:01/11:08:02 DRB1*11:11P 2 DRB1*11:11:01/11:11:02 DRB1*12:01P 6 DRB1*12:01:01/12:01:02/12:01:03/12:06/12:10/12:17 DRB1*12:02P 4 DRB1*12:02:01/12:02:02/12:02:03/12:02:04 DRB1*13:01P 7 DRB1*13:01:01/13:01:02/13:01:03/13:01:04/13:01:05/13:01:06/13:01:07 DRB1*13:02P 3 DRB1*13:02:01/13:02:02/13:02:03 DRB1*13:07P 2 DRB1*13:07:01/13:07:02 DRB1*14:01P 4 DRB1*14:01:01/14:01:02/14:01:03/14:54 DRB1*14:03P 2 DRB1*14:03:01/14:03:02 DRB1*14:05P 3 DRB1*14:05:01/14:05:02/14:05:03 DRB1*14:06P 2 DRB1*14:06:01/14:06:02 DRB1*14:07P 2 DRB1*14:07:01/14:07:02 DRB1*14:44P 2 DRB1*14:44:01/14:44:02 DRB1*15:01P 13 DRB1*15:01:01:01/15:01:01:02/15:01:02/15:01:03/15:01:04/15:01:05/15:01:06/15:01:07/15:01:08/15:01:09/15:01:10/ 15:01:11/15:01:12 DRB1*15:02P 7 DRB1*15:02:01/15:02:02/15:02:03/15:02:04/15:02:05/15:02:06/15:02:07 DRB1*15:03P 2 DRB1*15:03:01:01/15:03:01:02 DRB1*16:02P 2 DRB1*16:02:01/16:02:02 DQB1*02:01P 4 DQB1*02:01:01/02:01:02/02:02/02:04 DQB1*03:01P 9 DQB1*03:01:01/03:01:02/03:01:03/03:01:04/03:09/03:19/03:21/03:22/03:24 DQB1*03:02P 4 DQB1*03:02:01/03:02:02/03:02:03/03:02:04 DQB1*03:03P 2 DQB1*03:03:02/03:03:03 DQB1*04:01P 2 DQB1*04:01:01/04:01:02 DQB1*05:01P 2 DQB1*05:01:01/05:01:02 DQB1*05:02P 2 DQB1*05:02:01/05:02:02 DQB1*05:03P 2 DQB1*05:03:01/05:03:02 DQB1*06:01P 5 DQB1*06:01:01/06:01:02/06:01:03/06:01:04/06:01:05 DQB1*06:02P 2 DQB1*06:02:01/06:02:02 DQB1*06:03P 2 DQB1*06:03:01/06:03:02 DQB1*06:04P 7 DQB1*06:04:01/06:04:02/06:04:03/06:34/06:36/06:38/06:39 Groups were selected from the full list ( based on Table 3-7.

13 Lee KW, et al., New HLA Nomenclature (2010) 215 Table 10. HLA G groups selected for Koreans Group designation N of alleles in group Alleles within group Group designation N of alleles in group Alleles within group A*01:01:01G 8 A*01:01:01:01/01:01:01:02N/01:04N/ 01:22N/01:32/01:34N/01:37/01:45 A*02:01:01G 19 A*02:01:01:01/02:01:01:02L/ 02:01:01:03/02:01:08/02:01:11/02:01:14/ 02:01:15/02:01:21/02:09/02:43N/02:66/ 02:75/02:83N/02:89/02:97:01/02:97:02/ 02:132/02:134/02:140 A*02:05:01G 2 A*02:05:01/02:179 A*02:06:01G 2 A*02:06:01/02:126 A*02:07:01G 2 A*02:07/02:15N A*03:01:01G 9 A*03:01:01:01/03:01:01:02N/03:01:01:03/ 03:01:07/03:20/03:21N/03:26/03:37/03:45 A*11:01:01G 2 A*11:01:01/11:21N A*11:02:01G 3 A*11:02:01/11:02:03/11:53 A*23:01:01G 5 A*23:01:01/23:07N/23:17/23:18/23:20 A*24:02:01G 12 A*24:02:01:01/24:02:01:02L/24:02:03/ 24:02:10/24:02:13/24:02:31/24:09N/ 24:11N/24:40N/24:76/24:79/24:83N A*24:03:01G 2 A*24:03:01/24:33 A*25:01:01G 2 A*25:01:01/25:07 A*26:01:01G 4 A*26:01:01/26:01:07/26:24/26:26 A*29:01:01G 2 A*29:01:01:01/29:01:01:02N A*30:01:01G 3 A*30:01:01/30:01:02/30:24 A*30:02:01G 3 A*30:02:01/30:02:02/30:33 A*31:01:02G 3 A*31:01:02/31:14N/31:23 A*32:01:01G 2 A*32:01:01/32:01:02 A*33:03:01G 4 A*33:03:01/33:03:03/33:15/33:25 A*68:01:01G 2 A*68:01:01/68:01:07 A*68:01:02G 3 A*68:01:02/68:11N/68:33 B*07:02:01G 8 B*07:02:01/07:02:06/07:02:09/07:44/ 07:49N/07:58/07:59/07:61 B*07:05:01G 2 B*07:05:01/07:06 B*08:01:01G 2 B*08:01:01/08:19N B*13:02:01G 2 B*13:02:01/13:02:05 B*15:01:01G 8 B*15:01:01:01/15:01:01:02N/15:01:06/ 15:01:07/15:102/15:104/15:140/15:146 B*15:03:01G 2 B*15:03:01/15:103 B*15:12:01G 2 B*15:12/15:19 B*15:17:01G 2 B*15:17:01:01/15:17:01:02 B*18:01:01G 3 B*18:01:01/18:01:03/18:17N B*27:05:02G 3 B*27:05:02/27:05:04/27:13 B*35:01:01G 6 B*35:01:01/35:01:03/35:40N/35:42:01/ 35:57/35:94 B*35:03:01G 2 B*35:03:01/35:70 B*38:02:01G 2 B*38:02:01/38:18 B*39:01:01G 4 B*39:01:01:01/39:01:01:02L/39:01:03/ 39:46 B*40:01:01G 3 B*40:01:01/40:01:02/40:55 B*40:02:01G 3 B*40:02:01/40:56/40:97 B*40:06:01G 2 B*40:06:01:01/40:06:01:02 B*44:02:01G 5 B*44:02:01:01/44:02:01:02S/44:19N/44:27/ 44:66 B*44:03:01G 3 B*44:03:01/44:03:03/44:03:04 B*45:01:01G 2 B*45:01/45:07 B*46:01:01G 2 B*46:01:01/46:15N B*47:01:01G 2 B*47:01:01:01/47:01:01:02 B*48:01:01G 2 B*48:01:01/48:09 B*51:01:01G 8 B*51:01:01/51:01:05/51:01:07/51:11N/ 51:30/51:32/51:48/51:51 B*52:01:01G 2 B*52:01:01/52:07 B*54:01:01G 2 B*54:01/54:17 B*55:01:01G 2 B*55:01:01/55:01:03 B*55:02:01G 2 B*55:02:01/55:02:05 B*56:01:01G 2 B*56:01:01/56:24 B*57:01:01G 2 B*57:01:01/57:29 B*58:01:01G 3 B*58:01:01/58:01:04/58:11 B*81:01:01G 3 B*81:01/81:02/81:03 C*01:02:01G 3 C*01:02:01/01:02:02/01:25 C*01:03:01G 2 C*01:03/01:24 C*02:02:02G 2 C*02:02:02/02:29 C*03:02:01G 3 C*03:02:01/03:02:02/03:02:03 C*03:03:01G 3 C*03:03:01/03:20N/03:62 C*03:04:01G 3 C*03:04:01:01/03:04:01:02/03:04:03 C*04:01:01G 7 C*04:01:01:01/04:01:01:02/04:01:01:03/ 04:09N/04:28/04:30/04:41 C*05:01:01G 6 C*05:01:01:01/05:01:01:02/05:01:04/ 05:01:05/05:03/05:37 C*06:02:01G 3 C*06:02:01:01/06:02:01:02/06:02:03 C*07:01:01G 6 C*07:01:01/07:01:02/07:01:09/07:06/ 07:18/07:52 C*07:02:01G 6 C*07:02:01:01/07:02:01:02/07:02:01:03/ 07:50/07:66/07:74 C*07:04:01G 2 C*07:04:01/07:11 C*08:01:01G 4 C*08:01:01/08:20/08:22/08:24 C*12:02:01G 2 C*12:02:01/12:02:02 C*12:03:01G 4 C*12:03:01:01/12:03:01:02/12:03:06/12:23 C*15:02:01G 2 C*15:02:01/15:13 C*15:05:01G 3 C*15:05:01/15:05:02/15:05:03 DRB1*01:01:01G 2 DRB1*01:01:01/01:01:05 DRB1*03:01:01G 3 DRB1*03:01:01:01/03:01:01:02/03:01:08 DRB1*04:03:01G 2 DRB1*04:03:01/04:03:03 DRB1*04:05:01G 3 DRB1*04:05:01/04:05:03/04:05:04 DRB1*04:06:01G 2 DRB1*04:06:01/04:06:02 DRB1*04:07:01G 2 DRB1*04:07:01/04:07:03 DRB1*07:01:01G 2 DRB1*07:01:01:01/07:01:01:02 DRB1*08:01:01G 3 DRB1*08:01:01/08:01:03/08:01:05 DRB1*08:02:01G 2 DRB1*08:02:01/08:02:02 DRB1*08:04:01G 2 DRB1*08:04:01/08:04:04 DRB1*08:04:02G 2 DRB1*08:04:02/08:04:03 DRB1*11:01:01G 4 DRB1*11:01:01/11:01:02/11:01:06/ 11:01:08 DRB1*11:01:03G 2 DRB1*11:01:03/11:01:11 DRB1*11:04:01G 2 DRB1*11:04:01/11:04:02 DRB1*11:08:01G 2 DRB1*11:08:01/11:08:02 DRB1*11:11:01G 2 DRB1*11:11:01/11:11:02 DRB1*12:01:01G 4 DRB1*12:01:01/12:06/12:10/12:17 DRB1*14:01:01G 2 DRB1*14:01:01/14:54 DRB1*14:06:01G 2 DRB1*14:06:01/14:06:02 DRB1*14:07:01G 2 DRB1*14:07:01/14:07:02 DRB1*15:01:01G 2 DRB1*15:01:01:01/15:01:01:02 DRB1*15:02:02G 2 DRB1*15:02:02/15:02:05 DRB1*15:03:01G 2 DRB1*15:03:01:01/15:03:01:02 DQB1*02:01:01G 3 DQB1*02:01:01/02:02/02:04 DQB1*03:01:01G 7 DQB1*03:01:01/03:01:04/03:09/03:19/ 03:21/03:22/03:24 DQB1*06:01:01G 3 DQB1*06:01:01/06:01:03/06:01:05 DQB1*06:04:01G 5 DQB1*06:04:01/06:34/06:36/06:38/06:39 Groups were selected from the full list ( based on Tables 3-7.

14 216 Korean J Lab Med 2010;30: 접미사 G 는펩티드결합부위의염기서열이동일한 HLA 대립유전자의집합체를의미하는것으로, 각군에서최소숫자의대립유전자명칭의세번째영역끝에대문자 G를붙인다 (Table 10). 예를들어, A*02:01:01G는펩티드결합부위의염기서열이 A*02:01:01:01과동일한대립유전자들의집합체를의미하며 19개의대립유전자들이포함된다. 따라서, G군에는 1-2 영역의숫자는동일하지만 3-4 영역의숫자가다른대립유전자는포함되지않고 null 대립유전자는포함된다. G군에포함되는대립유전자의일부는 2 영역의숫자가다른것들도있는데, 이들은펩티드결합부위의염기서열은동일하지만그외부위의염기서열이다른것들이다 ( 예. A*01:01:01G군의 A*01:37과 A*01:45). Table 10에는한국인에서발견되는 HLA-A, -B, -C, -DRB1, -DQB1 대립유전자들을중심으로 G 군을선정하여나열하고, 해당 G 군에속하는현재까지알려진모든대립유전자를나열하였다. 2010년 3월말까지명명된 HLA class I과 class II 대립유전자를대상으로만들어진 P 와 G 군의종류와각군에포함되는대립유전자들의전체명단은 IMGT/HLA 데이터베이스웹사이트 ( 에제공되어있다. HLA DNA 명명법전환에대한제언 인터넷의발달및확대이용과함께정보공유의속도가매우빨라지고있고정보의국제교류가더욱활발해져 세계표준화 (global standard) 의중요성이강조되고있는실정이다. 특히, HLA 형별정보와함께조혈모세포기증의국제적교류가지속적으로증대되고있는현상황에서새로개정된 HLA DNA 명명법의국내정착은 HLA 분야에서의세계표준화에반드시필요한단계라고할수있다. IMGT/HLA 데이터베이스를비롯한 HLA 관련웹사이트에서는새로운명명법의정착을돕기위하여전환표와전환프로그램을제공하고있다. 그러나명명법전환에따른문제점발생을최소화하기위해서는이제까지사용해왔던명명법과새로개정된명명법을병용하는적응기가필요할것이다. 실제로미국의조혈모세포이식지원기관으로서 7백만명이상의조혈모세포기증희망자풀을확보하고있는 NMDP (National Marrow Donor Program) 의경우, 앞으로 1년간신 / 구두가지명명법의병행사용을허용하고 2011년 4월부터는새로운명명법만을사용하도록의무화할것이라고발표한바있다 (http: // 현재우리나라에도가족 중에서적절한기증자를확보하지못하는조혈모세포이식대상환자를위해조혈모세포기증희망자이십여만명이등록되어있으며, 수만단위의제대혈이보관되어있다 ( konos.go.kr). 이들에대한 HLA 데이터베이스를지속적으로보관 / 운영해야하는만큼, 우리나라도병용하는적응기를일정기간갖고, 이기간에새로운명명법전환에따른문제점을미리점검해보고완전한전환을위한준비를하여야할것이다. 즉, 관련분야전문인력을대상으로한홍보및교육, HLA 분석프로그램및 DB 운영프로그램개선, 신 / 구명명전환프로그램마련, HLA 검사보고서를포함한문서양식수정등에대한준비를하고실행에옮겨야할것으로생각된다. 참고문헌 1. Massey HD and McPherson RA. The major histocompatibility complex of man. In: McPherson RA, Pincus MR, eds. Henry s clinical diagnosis and management by laboratory methods. 21st ed. China: Saunders Elsevier, 2007: Thorsby E. A short history of HLA. Tissue Antigens 2009;74: WHO Nomenclature Committee. Nomenclature for factors of the HL-a system. Bull World Health Organ 1968;39: Terasaki PI and McClelland JD. Microdroplet assay of human serum cytotoxins. Nature 1964;204: Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, et al. Nomenclature for factors of the HLA system, Tissue Antigens 2010;75: Bodmer WF, Albert E, Bodmer JG, Dupont B, Mach B, Mayr WR, et al. Nomenclature for factors of the HLA system, In: Dupont B, ed. Immunobiology of HLA. New York: Springer-Verlag, 1989: Robinson J, Malik A, Parham P, Bodmer JG, Marsh SG. IMGT/HLA database--a sequence database for the human major histocompatibility complex. Tissue Antigens 2000;55: Lee KW, Yang SY. HLA-B22 diversity including a novel B54 variant (B*5507) in the Korean population. Hum Immunol 1999;60: Bodmer JG, Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Charron D, et al. Nomenclature for factors of the HLA system, Tissue Antigens 1997;49: Elsner HA and Blasczyk R. Immunogenetics of HLA null alleles: implications for blood stem cell transplantation. Tissue Antigens 2004;64:

15 Lee KW, et al., New HLA Nomenclature (2010) Cano P, Klitz W, Mack SJ, Maiers M, Marsh SG, Noreen H, et al. Common and well-documented s: report of the Ad-Hoc committee of the American society for histocompatiblity and immunogenetics. Hum Immunol 2007;68: Lee KW, Oh DH, Lee C, Yang SY. Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens 2005;65: Yi DY, Lee W, Huh JY, Hong SG, Jung B, Baek JY, et al. frequencies and haplotypic associations of 4,108 cord blood units in Korean by high-resolution sequence-based typing. Korean J Lab Med 2009(S2):S425. ( 이대영, 이우근, 허지영, 홍성근, 정보찬, 백진영등. 한국인제대혈 4,108 단위에서고해상도염기서열분석법에의한 HLA 대립유전자와일배체형빈도. 대한진단검사의학회지 2009( 부록2):S425.) 14. Song EY, Park H, Roh EY, Park MH. HLA-DRB1 and -DRB3 allele frequencies and haplotypic associations in Koreans. Hum Immunol 2004;65: Lee KW, Jung YA. Additional sequence analysis outside exon 2 clarifies DRB1*12 and DRB1*14 allelic frequencies in Koreans. Hum Immunol 2009;70: Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, et al. Nomenclature for factors of the HLA system, Tissue Antigens 2005;65: Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, et al. Nomenclature for factors of the HLA system, Tissue Antigens 2002;60: