中国人群与白种人群HLA~*02基因分布

作者对中国西双版纳傣族、上海地区汉族德国白人和土耳其白人四个群体进行了HLA-A~*02多位基因分析。应用2对引物和24个地高辛标记的探针可检出17个等位基因。结果表明两个中国群体A2等位基因分布与白人有明显差异,A~*0201是德国（90％）和土耳其（80％）人的主要等位基因,在汉族和傣族中则分别为40％与2.2％。同为中国人的傣族和汉族A02等位基因分布也显著不同,A~*0207是傣族的最常见等位基因。结果尚表明中国群体中A~*0207与B46强相关,傣族尤为明显,连锁不平衡多数达9.15。在傣族中与A~*02关联的单倍型以 A~*0207-B46-DR9为最常见。HLA-A~*02等位基因分布在不同群体、不同民族、不同地区的差异将对基础免疫研究及器官移植配型有重大意义。     

HLA-A02 subtyping in a Portuguese population

Allelic polymorphisms identified between HLA-A^*02 variants allow differentiation between potentially functionally different HLA molecules.

Given the differences in population distribution described in previous studies we aimed to evaluate the relative frequency of A^*02 alleles in Portuguese Caucasoids. The allele frequency of HLA-A^*02 has been defined by serology in this population at 26.6%.

Genomic DNA from 45 individuals from the central region of Portugal, previously assigned as HLA-A2 by serology, were studied using the HLA-A^*02 SSP ARMS-PCR subtyping kit provided within HLA Class I DNA typing component of the 12th IHW, which discriminates 17 different alleles.

HLA-A^*0201 was found the most frequent, present in 88.9% of this population although three other alleles were identified: A^*0205 (8.9%), A^*0207 (2.2%) and A^*0217 (2.2%). One A^*0205 sample was found in heterozygous combination with A^*0201. From 22 HLA-A^*02 related haplotypes analyzed, no significant association between HLA-A^*02 and other HLA alleles was seen. The haplotype HLA-A^*0201-B44-DRB1^*-DQA1^*0300-DQB1^*0301 was present in three samples and HLA-A^*0201-B14-DRB1^*01-DQA1^*0101-DQB1^*0501 and HLA-A^*0201-B51-DRB1^*11-DQA1^*0501-DQB1^*0301 were found in two individuals each. Similarly, HLA-A^*0205-B51-DRB1^*07-DQA1^*0201-DQB1^*0201 was seen in two out of four samples with HLA-A^*0205.

Even though the limited number of samples studied, A^*0201 frequency was similar to those reported for Caucasoid populations. In addition, A^*0207 allele previously found exclusively in Chinese populations and A^*0205, with a moderate significant frequency in African and North American Blacks, were described in this investigation.     

Heterogeneity of HLA-A2 in Asia-Oceanic populations

HLA-A2 is one of the most common yet most diversified HLA antigens with 17 subtypes so far identified at the molecular level. A2 subtyping may have significant impact on clinical medicines. We developed a PCR/SSO-based comprehensive typing protocol for HLA-A and investigated the distribution of A2 alleles in regional ethnic groups. A2 was detected with high frequencies in most study populations. A total of 480 A2+ samples were identified and subtyped. The gene frequencies of A2 ranged from 34% in Chinese, 29% in Australian Caucasoids, 21% in Polynesians, 14% in Javanese and 13% in Australian Aborigines. However, in Melanesians and Micronesians A2 was absent. Six A2 alleles were found in the present experiments including A^*0201, 0203, 0205, 0206, 0207 and 0210. In Aborigines all the A2+ donors were typed as 0201. In Caucasoids A^*0201 accounted for 95% of A2+ samples though other three subtypes A^*0203, 0205 and 0207 were also detected. Extraordinary A2 heterogeneity was observed in Asia-Pacific populations where A^*0201 has become a minority. In Chinese all the six A2 alleles were discovered with A^*0201, 0203, 0206 and 0207 as the four major ones. In Javanese A2 was equally divided into A^*0201, 0203 and 0206 while in Polynesians A2 is overwhelmingly dominated by the oriental A^*0206 (71%). Our study also showed that comprehensive DNA matching for A2 would eliminate most A mismatches in the unrelated-donor transplantation in study populations.     

Polymorphism of the promoter of the HLA-A locus

Of the first 350 bases upstream of the ATG signal sequences were obtained representing the following HLA-A locus alleles: A^*01, A^*0102, A^*02, A^*0202, A^*0206, A^*0207, A^*03, A^*0302, A11.2, A11.1, A^*68, A^*68011, A^*30, A^*3002, A^*23, A^*24, A^*26, A^*2602, A^*25, A^*29, A^*2902, A^*31, A^*31011, A^*32, A^*3201, A^*33, A^*3301, A^*3303, A^*34, A^*6601, A^*6602 A^*74, A^*80. We found 21 polymorphic positions of which a surprisingly large number (altogether 9) represent allele specific exchanges. For all 35 alleles tested of the HLA-A locus we found 16 different types of promoter. While all tested A2 subtypes, A^*0201, A^*0202, A^*0206, A^*0207 share the same promoter, there were in contrast several situations in which different subtypes of the same group have different promoters. This is true for HLA A^*01, A^*0102; A^*03, A^*0302; A^*30, A^*3002; A^*6601, A^*6602; A^*32, A^*3201; A^*29, A^*2902. Looking at the binding sites for nuclear factors, we observe that TATA-box, CAT-box, Enhancer B, the interferon response sequence and the Enhancer A (except HLA-A30 has one base exchange) are conserved within the HLA-A locus. The interferon response sequence shows for all A-locus alleles a double base pair exchange (TT for AC). In comparison with the promoter polymorphism of the HLA-B locus (Yao et al., 1995) we find a surprising diversity of the promoters in the HLA-A locus. While for the B-locus promoters large groups of sometimes strongly different alleles share the same promoter, in the HLA-A locus there is a private promoter for almost each allele and sometimes even each subtype. This lead to the conclusion that the promoter polymorphisms of the HLA-A and the HLA-B locus have been subjected to different selection pressure in evolution.     

HLA-A02 sub-typing by PCR-SSOP

HLA-A2 occurs at high frequencies in most populations. We have recently developed a PCR-SSOP typing method for the identification of HLA-A2 alleles. PCR primers selected from Intron 1 pos 126 → Exon 2 pos 5 and Exon 3 pos 273 → Intron 3 pos 13 selectively amplify 17 known allelic sub-types of HLA- A^*02, yielding a 828 bp fragment. 18 SSOP's, selected from Exon's 2 & 3 are used for the identification of alleles HLA-A^*0201-A^*0217. The method was applied to five populations and the % of individuals in each population with a specific HLA-A2 allele are given in the following table.

HLA-A^*0204,-A^*0208,-A^*0209, & -A^*0212 to 0217 were not detected in these populations. Whereas HLA-A^*0201 represented nearly all the HLA-A2 alleles in the two Caucasion populations and in the mixed Mexican population, this was not the case in the Chinese and Indian populations.     

Molecular analysis of HLA-A02 subtype frequencies in the population of Northern Italy

HLA-A^*02 is the most heterogenous HLA-A allele with seventeen molecular subtypes described so far. We have refined existing protocols for PCR-SSOP typing of these alleles by use of a single 1.6 Kb PCR-amplificate spanning the entire exons 2 and 3 as well as most of exon 4 of HLA-A^*02 genes. This allows direct screening for the presence of A^*0209 and A^*0215N, the only HLA-A^*02 subtypes with nucleotide substitutions in exon 4, without the need for two separate amplifications. A panel of twenty-four SSOPs was used to unequivocally discriminate all so far known A^*02 subtypes.

In order to assess the A^*02 subtype frequencies in the population of Northern Italy, a total of 101 HLA-A^*02 genes found in 92 healthy individuals from the Italian bone marrow registry have been analyzed so far. All these individuals were of Northern Italian origin. A total of 91 A^*02 genes typed as A^*0201 (90%) while six genes turned out to be A^*0205 (6%). A single allele typing as A^*0206, A^*0208, A^*0209 and A^*0217, respectively, was found (1% each). These data indicate that, while A^*0201 is by far the dominant A^*02 subtype in the population of Northern Italy, some rare A^*02 subtypes so far described only in ethnic groups other than Caucasians can occasionally be found. These findings suggest that molecular typing will redefine HLA-A^*02 subtype frequencies and may prove useful for optimal matching of HLA-A^*02⁺ donor-recipient pairs in unrelated bone marrow transplantation. They may also have implications on the selection of candidate patients for vaccination with HLA-A^*02 restricted peptide vaccines.     

A 0203 variant (A0203S) in thais

A total of 50 randomized individuals previously serologically and or DNA class I typed as A2 were studied for A2 subtypings by using 12 WS HLA-A^*02 subtyping DNA typing kit. The subjects were consisted of 44 Central Thai (CT) and 6 Thai-Muslim (TM). A2 subtypes found in this study were A^*0201 A^*0203, ^*0203S, ^*0206 ^*0207, ^*0209, ^*0210, ^*0211,^* 0216, ^*0217 and ^*02. The most common HLA A^*02 subtyping was A^*0203 which was 19 out of 44 (43.18%) A2 CT subjects and 4 of 6 (66.7%) TM. The ratios of A^*0203 : A^*0203S were 11:8 and 4:1 among CT and TM respectively. A^*0203S was found to be segregated in an informative family. The primer mix 513A yielded positive reaction with A^*0203 while negative reaction was observed for A^*0203S. Other primer mixes in the kit gave the same reactions for A^*0203 and A^*0203S.     

Allele typing of HLA-A10 group by nested-PCR-low ionic strength single stranded conformation polymorphism and a novel A26 allele (A26KY, A∗2605)

HLA-A26 is one of the most polymorphic HLA-A locus antigens among the Japanese population. Four HLA-A26 subtypes have so far been defined: A*2601– 2604 [1]. We developed a means of typing alleles of the HLA-A10 group by nested PCR low ionic strength single-stranded conformation polymorphism (NPCR-LIS-SSCP) that is simple and cost effective. We used it to type 200 DNA samples from unrelated Japanese individuals who were serologically HLA-A26 positive. We found a novel A26 allele that had been suggested by PCR-SSO. Sequence analysis of A26KY (officially assigned A^*2605, Accession No. D50068) revealed that the allele differs from A^*2601 by a single nucleotide substitution at position 299, which leads to an amino acid substitution Ala→Glu at position 76 in the a helix loop of the al domain. From our results, A^*2605 is likely to originate from A^*2601 by a single point mutation. HLA-A^*2601 showed the highest frequency (61.9%), followed by A^*2603 (19-5%), A^*2602 (17.6%), A^*2604 (0.5%), and A^*2605 (0.5%) in Japanese. Human Immunology 50, 140–147 (1996)     

脐血HLA-A位点PCR-SBT分型的研究

目的建立HLA—A位点等位基因的PCR-SBT高分辨分型方法，探讨DNA测序技术在脐血库样本HLA分型中的应用价值。方法利用PCR产物直接测序，对广州脐血库保存的547份脐血样本进行HLA—A位点2、3、4外显子的序列分析，由分型结果得出基因频率，与中华（上海）骨髓库北方人群、上海地区人群及德国白种人进行比较。结果采用PCR-SBT分型方法并结合分析软件确定了全部样本的HLA—A基因型，广州地区人群HLA-A等位基因以A＊110101（30．8％）最为常见，其后依次是A＊24020101／02L（16．18％）、A＊0207（11．88％）、A＊3303（9．42％）。A＊110101在广州汉族人群中出现的频率明显高于中华（上海）骨髓库北方人群，而A＊010101、A＊3001明显低于后者；在HLA-A2亚型人群中，A＊020101在广州、上海两地汉族人群中的频率明显低于德国白种人，而广州汉族人群中A＊020101与A＊0206均明显低于上海汉族人，但A＊0203明显高于后者。结论基于核酸序列测定的HLA分型技术能够直接、准确、快速地进行高分辨分型，将有助提高无亲缘关系供者脐血移植的临床效果。改进实验条件、升级分型软件，可以降低试剂成本和节约时间。     

Sequence analysis of two serological variants, HLA-A2K and HLA-A9HH, detected in Japanese

Two rare variants of HLA-A locus antigens, tentatively called HLA-A2K and HLA-A9HH, were serologically identified in the Japanese population. A2K and A9HH showed short reaction patterns of a series of anti-A2 and anti-A9 sera, respectively. The latter variant also reacted with some anti-A2 sera. Nucleotide sequences of full-length cDNAs for A2K and A9HH were determined. The results revealed that both antigens are encoded by previously undescribed alleles. The nucleotide sequence of the allele for A2K was identical to that of A^*0207 except for a single nucleotide difference in exon 3. The nucleotide sequence of the allele for A9HH was identical to that of A^*2402 except for two nucleotides in exon 2. These two nucleotides are shared by all the reported A2 alleles. These sequencing results the allele for A9HH were consistent with the serological cross-reactivity of A9HH with some anti-A2 sera.     

Analysis of putatative HLA-A homozygotes

HLA typing by molecular genotyping methods has become routine for class II typing and is now being pursued for class I typing. However, a deficiency in the DNA-based methodologies is the absence of information about cellular expression of the HLA molecule. This may be important in clinical HLA matching as we have identified two families with an HLA-A allele (A^*2402 and A^*0301 respectively) detected by DNA techniques but inherited as a serological “blank”. In an effort to determine the frequency of such HLA-blanks we have retrospectively analysed the HLA-A gene by PCR-SSO techniques from 200 serological HLA-A “homozygotes”.

In the 200 samples, 24 HLA-A heterozygotes were identified by PCR-SSO. These discrepancies were explained by: Two new alleles, A^*3004 and A^*24New were detected in this study. Another potential new allele, ??A^*7401 is under further investigation.

Overall, the study yielded no further examples of serologically “blank” HLA-A alleles and suggests that this is a relatively low frequency event. However, the results indicate that A2 subtypes and resolution of the A19 CREG are high priority targets for HLA-A genotyping.     

Role of strong anchor residues in effective binding of 10-MER and 11-MER peptides to HLA-A2402 molecules.

Analysis of the structural requirements for the interaction of antigenic peptides with HLA-A24 molecules are very important for studies of T cell recognition of various antigens, because HLA-A24 (A^*2402) is most common HLA-A allele in the world, especially in Oriental population. In order to precisely investigate the interaction of peptides with HLA-A24 molecules beyond previous analysis of self-peptides eluted from HLA-A24 molecules, we examined the A^*2402 interaction of 172 chemically synthesized 8-mer to 11-mer peptides carrying two residues (Try and Phe) at P2 and four residues (Phe, Trp, Leu and Ile) at their C-terminus by the use of stabilization assay. The results were statistically analyzed to assess the influence of anchor residues on peptide binding. The length of peptides (9- to 11-mer) did not affect A^*2402 binding except 8-mer peptides. Peptides possessing the aromatic residues at their C-terminus bound to A^*2402 molecules stronger than those bearing the aliphatic hydrophobic residues. These results indicate that two aromatic hydrophobic anchor residues permit the binding of longer peptides to A^*2402 molecules. Compared to our recent studies of B^*3501 and B^*5101 binding peptides, the present study suggested that both B and F pockets of A^*2402 molecules might be large and deep because these pockets favored bulky aromatic residues.     

Characterization of HLA-E polymorphism in four distinct populations in Mainland China

In this study, human leukocyte antigen (HLA)-E allelic typing was performed for 690 individuals from two southern Chinese Han populations (Hunan Han and Guangdong Han) and two northern Chinese populations (Inner Mongolia Han and Inner Mongolia Mongol) using polymerase chain reaction-sequence-specific priming (PCR-SSP) method. Our data showed that (1) HLA-E*01:01 and HLA-E*01:03, but not E*01:04 allele, were detected in the four populations, HLA-E distribution differed significantly between each of the two southern Chinese Han populations and the Inner Mongolia Mongol population, and between Hunan Han population and Inner Mongolia Han population; (2) HLA-G*01:05N-A*30-E*01:01-C*06-B*13:02-DRB1*07 was a conserved extended haplotype in the Chinese Han populations; (3) five HLA-A-E haplotypes showed significant linkage disequilibrium (LD) in at least one population, including HLA-A*02-E*01:03 in populations except for the Inner Mongolia Mongol group, HLA-A*01-E*01:01 and HLA-A*30-E*01:01 in the Hunan Han and the Inner Mongolia Han populations, HLA-A*33-E*01:01 in the two southern Chinese Han populations and HLA-A*03-E*01:03 in the Inner Mongolia Mongol group; and (4) Ewens-Watterson homozygosity test showed a trend for balancing selection at the HLA-E locus in each of the four populations. Our data unraveled the peculiarity in terms of HLA-E allelic and haplotypic repertoire in four main ethnic groups in Mainland China, findings shown here are valuable for future studies of the potential role of HLA-E in allogeneic organ transplantation and HLA-linked disease association in related ethnic groups.     

Detection of HLA-A66 in linkage disequilibrium with HLA-B41 in a significant number of individuals from Northern Italy

Among 2700 bone marrow donors from a local registry in Northern Italy, 416 carried HLA-A antigens belonging to the serological A-10 specificity. None of these could be unequivocally subtyped as A66 by serology. We have examined 34 A10+ samples (36 A10+ alleles) which presented differences in serological subtyping by molecular PCR-SSOP analysis. For this purpose, we used a previously described panel of sequence specific oligonucleotide probes that allows unequivocal subtyping of most A10 splits. 24 out of 36 A10 alleles analyzed was typed as A^*66. Assignement of the A^*6601 subtype was possible for 16 alleles; for the others, A^*6601 and A^*6602 could not be discriminated. In all cases except for one, the A^*66 allele was linked to HLA-B41 as determined by serology. Altogether, the A66/B41 haplotype was found in 63.8% of A10 alleles and in 0.85% of the total number of donors. We are currently performing family studies to confirm linkage disequilibrium between the two specificities.     

吉林汉族人群HLA-A高分辨基因的多态性分析*

背景：HLA与免疫遗传学、免疫生物学密切相关,其分型对于器官移植和非感染性疾病的易感性有重要意义。 目的：调查吉林汉族人群HLA-A位点基因多态性,分析不同人群HLA-A等位基因频率分布特征。 方法：采用基因测序技术检测2 196名吉林汉族人HLA-A位点第2、3、4外显子序列,软件分析得到分型结果,计算各等位基因频率并与不同人群进行比较。 结果与结论：共检测到42种HLA-A等位基因,其中3种等位基因频率≥5%,分别是HLA-A*02:01(8.5%),HLA-A*11:01(8.2%)和HLA-A*24:02(7.3%),这3种等位基因频率合计为24.0%。同时,检测到39种等位基因频率<0.5%的HLA-A等位基因,这39种等位基因频率合计为76.0%。吉林汉族人群HLA-A等位基因频率分布与美国亚裔人群、中国香港华人、日本人相比存在一定差异。提示吉林汉族人群HLA-A基因的分布有地域特征。      

Point mutation in the alpha helix of the HLA-C alpha2 domain generates a novel HLA-C allele,HLA-Cw*0106, in a Han Chinese individual in Taiwan

We report herein the identification of a new HLA-C allele using sequence-based typing (SBT). This novel allele, HLA-Cw*0106, was found in a Han Chinese individual from Taiwan. This individual was typed using SBT as having a class I HLA genotype of HLA-A*0206/0207, HLA-B*4601/5601, and HLA-Cw*0102/0106. This new allele differs from HLA-Cw*0102 in one of the nucleotides of the polymorphic exon 3 at codon 152 (GAG-->GTG; E152V). This residue is located in the alpha helix of the HLA-C alpha2 domain and may have the potential to affect the binding of HLA-C molecules with antigenic peptides and/or the interactions with the T cell receptor. This new allele was detected in a few individuals of Han Chinese in Taiwan, but has not yet been observed in the aboriginal populations in Taiwan.     

HLA-A*02 allele frequencies and haplotypic associations in Koreans

We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans.     

Polymorphism in the upstream regulatory region of the DQB1 gene (QBP) and four point (DRB1, QBP, DQA1, DQB1) haplotypes in the Dai minority population in China.

Using polymerase chain reaction and Dig-ddUTP labeled oligonucleotides we have investigated the DNA polymorphism for the DQB1 promoter region (QBP) and we have deduced four point haplotypes in 65 unrelated healthy individuals of the Dai minority population. A total of 8 QBP alleles were detected. The most frequent allele is QBP 5.11 with 87.7% allele frequency followed by QBP 3.21, 3.1, 5.12 with 33.8%, 23.1% and 15.4% allele frequency respectively. Four QBP alleles, 3.22, 3.32, 4.1 and 6.12 were absent in the Dai minority. The linkage disequilibrium of the QBP allele with certain DQB1 alleles was very strong. Complete positive association was found for QBP 2.1-DQB1^*0201, QBP3.1-DQB1^*0301, QBP6.11-DQB1^*0601. A total of 32 different four point haplotypes were deduced. Among them the most common haplotypes were DRB1^*1602, DQA1^*0102, QBP5.11; DQB1^*0502, DRB1^*1602-QBP5.11, DQA1^*0102, DQB1^*0502 (N = 19); DRB1^*09 DQA1^*03, QBP3.21, DQB1^*03032 (N = 5); DRB1^*1401, DQA1^*01, QBP5.11, DQB1^*0502 (N = 12) and DRB1^*1202, DQA1^*0601, QBP3.1, DQB1^*0301 (N = 10). We conclude from these data that a) there is a reduced class II polymorphism in the Dai minority population an b) the relationship between QBP and DQB1 alleles is not different from that observed in other populations.     

HLA-C allele frequencies and linkage disequilibrium in 604 random Caucasian donors by high resolution PCR-SSP.

Sequence-specific PCR (PCR-SSP) methods have been successfully used to type HLA-C to a medium resolution level through the use of group-specific amplifications. We have developed high resolution PCR-SSP utilising 48 allele and group-specific PCR reactions to define HLA-C to the allelic level in order to find out the true level of polymorphism in a random Caucasian population and hence define the linkage disequilibrium between HLA-A, HLA-B and HLA-C.

604 consecutive samples from random individuals consisting of 552 cadaver donors and 52 random blood donors were typed by high resolution PCR-SSP. The PCR conditions and parameters are described in Tissue Antigens 95, vol. 46 pg 355. Cw^*0101, ^*0201, ^*0302, ^*0402/3, ^*0703, ^*0801/3, ^*1201,^* 1301, ^*1401,^* 1403 ^*1501/3/4 were not detected in our population although we have detected Cw^*0302, ^*1403, ^*0801 and ^*1504 in other populations. Cw7 is the most common Caucasian HLA-C antigen with frequencies of 30, 28 and 3.8% for Cw^*0701,^* 0702 and ^*0704 respectively. Cw^*0701 is in linkage disequilibrium with B8, B49 and B18, Cw^*0702 is associated with B7 and B39 whilst Cw^*0704 is associated with B44 and B^*1518. Complete frequencies, linkage disequilibria, statistics and full information on the primer mixes will be given.     

Identification of HLA-B44 and HLA-B45 alleles using a nested arms-PCR method

The establishment of DNA based identification of HLA Class I specificities has made high resolution typing possible at the allelic level. With such methods, it is feasible to identify population variation in allelic frequencies. Working towards higher allelic resolution of the HLA Class I loci we have developed a panel of primers to identify all the known HLA-B^*44 alleles and B^*4501 using a nested ARMS-PCR approach. There are currently seven different B^*44 alleles identified: B^*4402, B^*44031, B^*44032, B^*4404, B^*4405, B^*4406 and B^*4407. The system was validated using DNAs from B lymphoblastoid cell lines which have been sequenced for their B^*44 alleles. Further typing has been performed on a panel of 29 cell lines from the IHW cell panel and some 37 samples collected as part of the anthropological study of the Orkney islanders, all of which were previously defined as being B^*44 by the 12th Workshop HLA Class I typing kit. In the Orcadian population B^*4402 was found in 28 individuals to be the most common B^*44 allele, with 18 of these individuals expressing the A^*02-Cw^*0501-B^*4402 haplotype. The remaining 9 B^*44 positive individuals were all found to express the A^*29-Cw^*1601-B^*44031 haplotype. Methods and results will be presented.