DPB1 Loci Research Articles

Effect of human leukocyte antigen homozygosity on rubella vaccine–induced humoral and cell-mediated immune responses

Human leukocyte antigen (HLA) genes play a critical role in host immunity, including vaccine responses. HLA molecules present antigenic peptides to T cells and provide inhibitory signals to NK cells, and polymorphisms within HLA genes allow binding and presentation of a diverse array of self and foreign peptides. Heterozygosity across HLA alleles has been found to play a positive role in host defense for a variety of infections. Homozygosity within one or more HLA loci may restrict this epitope repertoire and limit T-cell responses to infection or vaccination. Here we report that homozygosity within the HLA DPB1 locus is associated with increased levels of rubella-specific IgG, an effect driven by a common allele DPB1*0401. We also show that homozygosity within different HLA class I and class II loci is correlated with variations (but not necessarily decreases) in interleukin (IL)–2, IL-5, and IL-10 secretion after rubella virus stimulation.

Polymorphism of HLA-DRB1, -DQB1 and -DPB1 genes in Bai ethnic group in southwestern China

In this work, polymorphism of human leukocyte antigen (HLA)-DRB1, -DQB1 and -DPB1 genes was detected using polymerase chain reaction-sequence-based typing method in 128 healthy unrelated volunteers from the Bai ethnic group of Yunnan province of southwest China. Among all the 28 alleles detected for the DRB1 gene, the most common allele was DRB1*120201 with a frequency of 16.41%, followed by DRB1*090102, DRB1*080302, DRB1*1404, DRB1*150101, DRB1*140101 and DRB1*160201, with frequencies of 10.16%, 9.77%, 9.38%, 8.98%, 8.59% and 8.21%, respectively. Among 19 DQB1 alleles detected, the most frequent allele was DQB1*030101/0309 (35.94%), followed by DQB1*050201 (11.33%), DQB1*060101/060103 (10.54%) and DQB1*0401 (10.16%). For the DPB1 locus, the most common alleles were DPB1*0501 (42.19%), DPB1*1301 (13.28%), DPB1*020102 (10.93%) and DPB1*040101 (9.77%). The comparison of HLA class II allele frequencies of Bais with those of other Chinese populations suggested that the Bai ethnic group belonged to the southern group of Chinese.

Anti-Cofactor Autoantibodies in Systemic Lupus Erythematosus: Prevalence, Clinical and HLA Class II Associations

The aim of our study was to evaluate the clinical and HLA-class II allele associations of some anti-cofactor antibodies in a homogeneous group of European patients with SLE. One hundred thirty-six patients with SLE, fulfilling four or more of the ACR 1997 revised criteria for the classification of the disease, coming from 7 European countries, were enrolled consecutively. Anti-prothrombin (anti-PT), anti-annexin V (anti-AnnV), anti-protein C (anti-Cprot) and anti-protein S (anti-Sprot) were determined by using commercial ELISA kits. Molecular typing of HLA-DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 loci was performed by using PCR-SSOP method, carried out using digoxygenin (DIG) labeled probes. The prevalence of anti-AnnV, anti-PT, anti-Cprot and anti-Sprot was 19%, 10.4%, 4.4% and 8.1%, respectively. Twenty-seven % of anti-AnnV positive patients reported migraine vs 5.5% of anti-AnnV negatives (p = 0.003, but p not significant, odds ratio (OR) = 6.4, 95% confidence interval (CI) = 2–21). Anti-PT, anti-AnnV and anti-Sprot were positively associated with some HLA alleles, but pc was not significant. In this study we have shown that some HLA alleles carry the risk to produce antibodies against phospholipid-binding proteins, but these association need confirmation in other studies, because they have never been reported and appear to be weak associations.

HLA‐DPB1 polymorphism in Blang and Puyi ethnic groups of Southwest China inferred from sequence‐based typing

In the present study, DNA typing for HLA-DPB1 was performed using polymerase chain reaction (PCR)-sequence-based typing method in two isolated Chinese populations: the Blangs (n = 94) in Shuangjiang County and the Puyis (n = 76) in Luoping County from Yunnan province of Southwest China. These two populations exhibited certain similarity in their allelic distributions of the HLA-DPB1 gene. A total of 11 and 12 alleles at the DPB1 locus were found in the Blang and Puyi groups, respectively. In the Blang group, the most frequent alleles were DPB1*0501 (51.0%) and DPB1*1301 (17.0%). DPB1*030101 was also common with a frequency of 6.4%. In the Puyi group, the most frequent allele was also DPB1*0501 with a frequency of 47.5%, followed by DPB1*1301 (21.1%). Two alleles DPB1*2101 and DPB1*0202 followed, with frequencies ranging between 5% and 8%. The alleles DPB1*4101, DPB1*3301, DPB1*6801 and DPB1*8401 were found for the first time in Chinese populations. A dendrogram constructed by neighbor-joining method showed that the Blang and Puyi ethnic minorities, which had the closest relationship belonged to the southern Chinese.

HLA-DPB1*0402 Protects Against Type 1A Diabetes Autoimmunity in the Highest Risk DR3-DQB1*0201/DR4-DQB1*0302 DAISY Population

A major goal in genetic studies of type 1A diabetes is prediction of anti-islet autoimmunity and subsequent diabetes in the general population, as >85% of patients do not have a first-degree relative with type 1A diabetes. Given prior association studies, we hypothesized that the strongest candidates for enhancing diabetes risk among DR3-DQB1*0201/DR4-DQB1*0302 individuals would be alleles of DP and DRB1*04 subtypes and, in particular, the absence of reportedly protective alleles DPB1*0402 and/or DRB1*0403. We genotyped 457 DR3-DQB1*0201/DR4-DQB1*0302 Diabetes Autoimmunity Study of the Young (DAISY) children (358 general population and 99 siblings/offspring of type 1 diabetic patients) at the DPB1, DQB1, and DRB1 loci using linear arrays of immobilized sequence-specific oligonucleotides, with direct sequencing to differentiate DRB1*04 subtypes. By survival curve analysis of DAISY children, the risk of persistently expressing anti-islet autoantibodies is approximately 55% for relatives (children with a parent or sibling with type 1 diabetes) in the absence of these two protective alleles vs. 0% (P = 0.02) with either protective allele, and the risk is 20 vs. 2% (P = 0.004) for general population children. Even when the population analyzed is limited to DR3-DQB1*0201/DR4-DQB1*0302 children with DRB1*0401 (the most common DRB1*04 subtype), DPB1*0402 influences development of anti-islet autoantibodies. The ability to identify a major group of general population newborns with a 20% risk of anti-islet autoimmunity should enhance both studies of the environmental determinants of type 1A diabetes and the design of trials for the primary prevention of anti-islet autoimmunity.

Class II HLA allele polymorphism: DRB1, DQB1 and DPB1 alleles and haplotypes in the New Zealand Maori population

Class II alleles of interest to transplantation comprise the DRB1, DQB1 and DPB1 loci. Sequence-based typing was used to determine the class II allelic variability present in New Zealand Maori, a population with close genetic ties to Polynesia and known anthropological and linguistic connections to mainland Asia. The most common DRB1 alleles identified were DRB1*1201, DRB1*110101, DRB1*0403 and DRB1*080302, with frequencies of 21.5%, 14%, 11.25% and 9.25%, respectively. Standard linkages between the DRB1 locus and the DRB3, 4 and 5 loci were maintained, with no novel patterns identified. The most common DQB1 alleles identified were DQB1*030101, DQB1*060101, DQB1*020101, DQB1*0602 and DQB1*050201, with frequencies of 29.5%, 8%, 7.8%, 6.4% and 6.2%, respectively. The most common DPB1 alleles identified were DPB1*0501, DPB1*040101 and DPB1*020102, with frequencies of 40.2%, 28.89% and 15.83%, respectively. A total of 80 estimated DRB1-DQB1 two-locus haplotypes were detected. DRB1*1201-DQB1*030101 was the most frequent (15.40%) haplotype, followed by DRB1*110101-DQB1*030101 (9.97%), DRB1*0403-DQB1*030201 (7.37%) and DRB1*080302-DQB1*060101 (5.96%). The allelic variation determined is being used in further analysis of the requirement for bone marrow transplantation in the New Zealand Maori population and has implications for optimal ethnic donor distribution on the New Zealand Bone Marrow Donor Registry, anthropological studies and disease association.

Importance of HLA-DQ and HLA-DP polymorphisms in cytokine responses to naturally processed HLA-DR-derived measles virus peptides

We studied the association between class II human leukocyte antigen (HLA)-DRB1*0301 presented measles virus (MV) peptide-specific cytokine responses and DQB1 and DPB1 alleles among 313 individuals who received two doses of measles–mumps–rubella-II vaccine. The overall median IFN-γ secretion levels (first and third quartiles) for the 19-amino acid MV phosphoprotein (MV-P)- and 14-amino acid MV nucleoprotein (MV-N)-derived peptides were 27.7 pg/ml (1.8, 109.4) and 1.9 pg/ml (−6.2, 13.0), respectively; median IL-4 secretion levels were −0.6 pg/ml (−7.1, 6.2) and 2.4 pg/ml (−3.2, 9.3), respectively. Primary statistical analyses were adjusted for previously identified DRB1 associations. A marginally significant increase in the frequency of the DQB1*0604 ( p = 0.02) allele was found among subjects who demonstrated detectable IL-4 levels to the MV-P peptide. Further, DPB1*0201 ( p = 0.02) and DPB1*1301 ( p = 0.09) alleles provided suggestive evidence of an association with MV-P-induced IL-4 secretion. Examination of IFN-γ responses to MV-P and MV-N indicated that none of the individual alleles of the DQB1 and DPB1 loci were associated with peptide-induced T cell response. An increase in the frequency of DPB1*0501 ( p = 0.01) was found among subjects who failed to produce MV-N peptide-specific IL-4 responses. These data further confirm that HLA-DRB1 alleles are the major restriction molecules for MV-P and MV-N measles virus antigen presentation to T cells. We speculate that MV-P and MV-N peptides derived from DRB1*0301 could potentially be recognized in association with different HLA molecules, including DQB1 and DPB1; however, statistical adjustments for the effect of HLA-DR locus could potentially alter these genetic relationships. This concept provides important information supporting the use of promiscuous peptides in a peptide-based vaccine approach.

Novel cynomolgus macaque MHC‐DPB1 polymorphisms in three South‐East Asian populations*

Cynomolgus macaques (Macaca fascicularis, Mafa), alias the crab-eating monkeys or long-tailed macaques, live across a vast range of South-East Asia. These non-human primates have emerged as important animal models in infectious and chronic diseases and transplantation studies, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphic variation or diversity of the Mafa-DPB1 locus is largely limited in comparison with the more commonly studied rhesus macaque DPB1 locus. In this article, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-DPB1 locus among three South-East Asian populations and to investigate how the allele differences between macaques and humans might affect their respective immune responses, we identified 40 alleles within exon 2 of the Mafa-DPB1 locus by DNA sequencing using 217 individuals. We also performed evolutionary and population analyses using these sequences to reveal some population-specific alleles and trans-species allelic conservation between the cynomolgus macaques and the rhesus macaques. Of the 40 new alleles, eight belong to a newly identified lineage group not previously found in the rhesus macaque species. This allele information will be useful for medical researchers using the cynomolgus macaques in disease and immunological studies.

Polymorphism of the DPB1 locus in Hani ethnic group of south‐western China

Polymorphism of HLA-DPB1 was revealed with a sequencing-based typing (SBT) method in 47 unrelated healthy individuals from Yunnan Hani ethnic minority. The alleles DPB1*5901 and DPB1*7001 were detected for the first time in Chinese populations. A dendrogram showed that the Hani ethnic group belongs to the southern group of Chinese.

Interaction of loci within the HLA region influences multiple sclerosis course in the Sardinian population

We examined the influence of alleles at the HLA loci, previously found to be associated with multiple sclerosis (MS) in Sardinia, on the clinical course of the disease in 835 relapsing (R) and 100 primary progressive (PP) patients. Multivariate analysis was carried out on predisposing 0301 or non-associated DPB1 alleles, susceptible or non-associated DRB1-DQB1 haplotypes, both predisposing and non-predisposing, and negatively and non-negatively associated D6S1683 alleles, taking interaction between them into account. Intra-patient analysis showed that the presence of the susceptible or protective D6S1683 allele interacting with predisposing DP 0301 modulated risk of PP disease. These findings suggest that a locus telomeric to HLA class I exerts an effect on alleles at the DPB1 locus in modulating disease course.

TAP1 and TAP2 Gene Polymorphisms and HLA-TAP Haplotypes in Koreans Based on 90 Families

We have investigated the polymorphism of TAP genes and the distribution of human leukocyte antigen ( HLA)- TAP haplotypes in 90 Korean families (180 parents and 233 children), previously typed for HLA class II alleles. TAP1 (codons 333 and 637) and TAP2 (codons 379, 565, 577, 651, 665, and 687) typings were carried out by use of polymerase chain reaction–restriction fragment length polymorphism method. For TAP1, four alleles (gene frequency: A 81.9%, B 15.0%, C 2.5%, D 0.5%) and for TAP2, nine alleles ( A1 31.7%, A2 14.2%, B 32.5%, Bky2 6.1%, C 6.9%, D 2.5%, E 3.9%, G 0.8%, and H 1.4%) were detected. Sixteen different TAP1-TAP2 haplotypes were observed with frequencies > 0.5%, and we found that significant linkage disequilibrium was present between TAP1 and TAP2 loci ( p < 0.001). When HLA-DRB1-DQB1 haplotypes were extended to TAP1 and TAP2 loci, much diversification of haplotypes was observed: 26 different DRB1-DQB1 haplotypes (frequencies > 0.8%) formed 90 different extended haplotypes. Eight recombinant haplotypes between DQB1 and DPB1 loci were observed, and most (seven of eight) of the recombinations occurred between TAP2 and DPB1 loci. These results add more evidence to the view that recombination hot spot is present within and around TAP gene region.

The DR4–DQ8 haplotype and a specific T cell receptor Vβ T cell subset are associated with absence of allergy to Can f 1

The significance of specific T cell receptor (TCR) Vbeta subtypes and human leucocyte antigen (HLA) class II alleles for the development of allergy to lipocalin allergens such as the major dog allergen Can f 1 is not clear at present. To characterize the TCR Vbeta usage in the Can f 1-specific T cell lines and the HLA class II genotypes of Can f 1-allergic and non-allergic subjects. T cell lines were induced with recombinant Can f 1 from the peripheral blood mononuclear cells of 12 non-atopic dog owners and 26 dog-allergic patients. Thirteen of the dog-allergic subjects were sensitized to Can f 1. Expression of the TCR Vbeta subtypes on CD4(+) T cells in the T cell lines was measured by flow cytometry. The subjects were HLA genotyped for DRB1, DQB1 and DPB1 loci. Can f 1-specific T cell lines were obtained from 18 subjects, with either positive (n=8) or negative (n=10) skin prick tests (SPTs) to recombinant Can f 1. The frequency of TCR Vbeta5.1(+) T cells was significantly higher in the T cell lines of subjects with negative SPTs to the allergen. Moreover, DR4-DQ8 haplotype was over-represented among these subjects. The DR4-DQ8 haplotype and the TCR Vbeta5.1(+) CD4(+) T cells may be protective against allergy to Can f 1.

Association of clinical features with HLA in chronic pulmonary thromboembolism

The aetiology of chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown and may be heterogeneous, because there are several ethnic differences in the clinical characteristics of CTEPH. Female predominance and a higher ratio of chronic to acute pulmonary thromboembolism have been reported in Japan as compared with the USA. Because such ethnic differences may be controlled by genetic factors, the current study investigated HLA polymorphisms in Japanese patients with CTEPH. HLA typing by serological and/or DNA typing methods was performed (for HLA-A, B, DPB1, DRB1) in 80 patients and 678 controls, and the association of clinical characteristics with HLA alleles was studied. The frequencies of HLA-B*5201 (40 versus 24%) and DPB1*0202 (19 versus 6%) were significantly higher in the patients. HLA-B*5201 positive patients showed a significant female predominance. Total pulmonary vascular resistance and mixed venous oxygen tension were better in the HLA-B*5201 positive patients. In contrast, cardiac index and gas exchange parameters were worse in the HLA-DPB1*0202 positive patients. In the patients carrying HLA-B*5201 and/or -DPB1*0202, the frequency of deep vein thrombosis was significantly lower than the other patients. These observations suggested that both the susceptibility and clinical characteristics of chronic thromboembolic pulmonary hypertension were controlled in part by the HLA-B and -DPB1 loci.

DPB1 alleles are associated with type 1 diabetes susceptibility in multiple ethnic groups.

Genetic associations between type 1 diabetes and alleles at the HLA class II locus DPB1 have been previously reported. Observed associations could be due to variation in the DPB1 locus itself or to linkage disequilibrium (LD) between DPB1 alleles and other susceptibility loci. One measure of whether the association of an allele with a disease reflects a true effect of the locus or is simply due to LD is the observation of that association in multiple ethnic groups. Previous type 1 diabetes associations have been reported for DPB1*0301 and DPB1*0202 (predisposing) and for DPB1*0402 (protective). In this study, results are reported from testing these associations in three different sample sets: 1) Puerto Rican case and control subjects, 2) Mexican-American simplex families, and 3) high-risk (DR3/DR4) individuals with and without an affected relative. DPB1*0301 was associated in all three groups, even after accounting for LD with DRB1-DQB1. DPB1*0202 and DPB1*0402 were positively and negatively associated, respectively, in two of the three populations. These results suggest that the observed DPB1 associations, especially that of the DPB1*0301 allele, with type 1 diabetes are likely to be true associations. This supports the concept that multiple genes in the HLA region can affect type 1 diabetes susceptibility.

Genetic polymorphism and linkage disequilibrium of the HLA-DP region in Basques from Navarre (Spain).

In this work, a sample of 116 individuals from an autochthonous Basque population (northern Navarre, Spain) was typed at the DNA level for HLA-DPA1 and HLA-DPB1 loci, with the aim of analysing the genetic polymorphism and the linkage disequilibrium (LD) of the HLA-DP region. In this Basque subpopulation, the most frequent alleles were *0103 (0.767) and *0201 (0.185) for DPA1 locus, whereas for DPB1 locus the *0401 allele was predominant (0.307). Accordingly, the most frequent haplotype was DPA1*0103-DPB1*0401 (0.300), which showed a significant LD. However, the haplotypes that most differentiated the sample of Navarre from other worldwide populations already analysed were DPA1*0105-DPB1*1901 (0.011) and DPA1*0201-DPB1*7601 (0.021), both of which showed a strong LD. Analysis of the relationships between populations based on data provided by HLA-DPA1 and HLA-DPB1 loci revealed a high genetic affinity between the Basque samples (North Navarre and Guipúzcoa), which, in turn, tend to plot separately from the remaining European populations. Gene frequency clines for DPB1*01, DPB1*04 and DPB1*11 alleles among European populations are reported for the first time. These alleles showed maximum values of F(ST) (0.033, 0.034 and 0.025, respectively). Various evolutionary forces were considered in discussing the origin of the spatial structuring of the gene frequencies: (i) gene flow, argued from the hypotheses of Post-glacial recolonization from southern Europe or the demic diffusion of farmers from the Near East into Europe, and (ii) the existence of selective pressures that could have generated genetic microdifferentiation.

HLA Class II Variation in Indigenous Populations from Thailand

We have a lysed the distribution of class II alleles in five populations from Thailand, by PCR amplification of second exon of the DRBl, DQA1, DQB1 and DPB1 loci and typing using non adioactive sequence-specific oligonucleotide probes. Extensive allelic variation was found at all four loci examined, but no new alleles were identified. The allele frequency distribution was very similar among the Thai populations, indicative of limited amounts of genetic divergence among the different populations examined. A phylogenetic a lysis was conducted using the allele frequency data for each locus to study the relationships between Thai populations, other Asian populations and populations from other parts of the world. In the phylogenetic trees for three of the four loci, the Thai populations cluster with other Asian populations, supporting the similarity among Asian populations. The branch lengths of the phylogenetic trees are substantially longer for the DQA1 and DQB1 loci, as compared to DRB1 and DPB1 loci. In particular, the length of branches separating populations on different continents are more pronounced for the DQA1 and DQB1 loci.

High resolution sequence-based DPB1 typing identified two novel DPB1 alleles, DPB1*9401 and DPB1*9501, from a Kenyan population.

Two novel DPB1 alleles, DPB1*9401 and DPB1*9501, were identified from a Kenyan population during sequence-based HLA-DPB1 typing. Molecular cloning and sequencing of multiple clones confirmed that one of the new DPB1 alleles is identical to DPB1*0402 at exon 2 except for a single nucleotide substitution (CGG -->TGG), changing codon 70 from Arg to Trp. The new allele has been named DPB1*9401. This is the first report of polymorphism at codon 70 of HLA-DPB1 alleles. New codon combinations have been identified in another novel DPB1 allele named DPB1*9501. The extensive diversity at DPB1 locus of this East African population is being revealed by high resolution sequence-based DPB1 typing.

Inheritable variable sizes of DNA stretches in the human MHC: conserved extended haplotypes and their fragments or blocks.

The difference in sizes of conserved stretches of DNA sequence within the major histocompatibility complex (MHC) in human individuals constitutes an underappreciated genetic diversity that has many practical implications. We developed a model to describe the variable sizes of stretches of conserved DNA in the MHC using the known frequencies of four different kinds of small (< 0.2 Mb) blocks of relatively conserved DNA sequence: HLA-Cw/B; TNF; complotype; and HLA-DR/DQ. Each of these small blocks is composed of two or more alleles of closely linked loci inherited as one genetic unit. We updated the concept of the conserved extended haplotype (CEH) using HLA allele identification and TNF microsatellites to show that specific combinations of the four blocks form single genetic units (>/= 1.5 Mb) with a total haplotype frequency in the Caucasian population of 0.30. Some CEHs extend to the HLA-A and -DPB1 loci forming fixed genetic units of up to at least 3.2 Mb of DNA. Finally, intermediate fragments of CEHs also exist, which are, nevertheless, larger than any of the four small blocks. This complexity of genetic fixity at various levels should be taken into account in studies of genetic disease association, immune response control, and human diversity. This knowledge could also be used for matching CEHs and their fragments for patients undergoing allotransplantation.

HLA-DPB1*0401 is associated with dominant protection against type 1 diabetes in the general Saudi population and in subjects with a high-risk DR/DQ haplotype.

The human leukocyte antigen (HLA) class II DQB1*0201/0202-DRB1*04 genotype has been identified as predisposing to type 1 diabetes [insulin-dependent diabetes mellitus (IDDM)] in the Saudi Arabian population (P = 0.0002; odds ratio = 0.67; 95% confidence interval = 0.009-0.381). In this study, we searched for a factor at the DPB1 locus by analysing DPB1 polymorphism using sequence-based typing in 86 Saudi IDDM patients and control subjects, all carrying the HLA-DRB1*04/DQB1*02 haplotype or the known susceptibility allele DQB1*0201/0202. Significant protection was conferred by DPB1*0401, which was observed in 17 of 50 control subjects (55%) and 2 of 36 IDDM patients (5%) with the DQB1*0201/0202 allele (P = 0.0012; odds ratio = 8.75; confidence interval = 1.72-59.70). Our data showing a high frequency of the DPB1*0401 allele even in the presence of the predisposing DQB1*02 allele in healthy subjects may indicate a protective effect of this combination of HLA alleles against type 1 diabetes. This finding supports the hypothesis that protective HLA class II genes can override the risk conferred by HLA-DQ susceptibility alleles. Further studies using larger cohorts of control subjects and patients should be undertaken to confirm this observation.

HLA-DRB1, DQB1 and DPB1 polymorphism in the Naxi ethnic group of South-western China.

Polymorphism of HLA-DRB1, DQB1 and DPB1 was revealed with a sequencing-based typing (SBT) method in unrelated healthy volunteers from the Naxi ethnic group. Among the 43 DRB1 alleles detected, the most common allele was DRB1*12021 with a frequency of 17%, followed by DRB1*08032, DRB1*09012 and DRB1*1404 with frequencies of 8.5%, 7.4% and 7.4%, respectively. Among 23 DQB1 alleles detected, the most frequent DQB1 allele was DQB1*03011/0309 (21.9%), followed by DQB1*0502 (16.4%) and DQB1*05031 (9.6%). For the DPB1 locus, the most common alleles were DPB1*0501 (25.5%), DPB1*0402 (14.6%) and DPB1*02012 (12.0%). The most common DRB1-DQB1-DPB1 haplotype was DRB1*1404-DQB1*05031-DPB1*0402 with a frequency of 5.26%, followed by the DRB1*08032-DQB1*06011-DPB1*1301 (3.51%). The distribution characteristics of the HLA class II alleles revealed that the Naxi ethnic group belonged to the Southern group of Chinese.