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There is no doubt that HLA-DR molecules are acting as the products of HLA-linked immune response genes (Ir-genes), because (i) HLA-DR molecules are the restriction elements in the interaction between CD4+ helper T cells and antigen-presenting cells (APC) to respond to many antigens such as streptococcal cell wall antigen (SCW) (Nishimura & Sasazuki, 1983; Sone et al., 1985; Hizayama et al., 1986), schistosomal antigen (Sj) (Hirayama et al., 1987), Mycobacterium leprae antigen (ML) (Kikuchi et al., 1986) and so on; and (ii) anti-HLA-DR monoclonal antibodies completely abolish the immune response to those antigens (Nishimura & Sasazuki, 1983; Sone et al., 1985). However, genetic analysis of the immune response to those antigens in families or populations revealed that responsiveness is recessive and non-responsiveness to those antigens is a dominant genetic trait that is tightly linked to HLA (Sasazuki et al., 1980a, 1983; Watanabe et al., 1988). This is completely opposite to the situation under the Ir-gene control where responsiveness is dominant and non-responsiveness is recessive. In this paper, we report evidence of how we came across the concept of HLA-linked immune suppression genes (Is-genes) besides Ir-genes, and show evidence for the epistatic interaction between HLA-DR and DQ to determine the immune response to several antigens in humans. [ABSTRACT FROM AUTHOR]

With a view to establishing an accurate evaluation of the genetic predisposition to insulin-dependent type I diabetes (IDDM), we have built a model based on the characteristics of the relevant pockets of HLA-DR and -DQ molecules. Three independent populations were investigated. Group I and group II were Caucasoids, while group III was Japanese, including a total of 1,166 IDDM patients and 2,391 healthy controls. We formulate the hypothesis that suceptibility to IDDM is not only explained by the absence of Aspartate 57 (negative charge) from pocket 9 of DQB1 (P9DQ), but also by the presence of an electric charge (+/- vs. neutral), generated by residues 70, 71 and 74 in pockets 4 of DRB1 (P4DR) and DQB1 (P4DQ) molecules. The respective weight of each pocket, was evaluated in a multivariate analysis based on the logistic regression method. The 4 components (2 loci and 2 pockets) were systematically analysed in the computer model. It was clearly shown that the structural characteristics of pockets P9DQ-P4DR and, to a lesser degree that of P4DQ, account for IDDM predisposition. On applying the model to the whole international series, it appears that the highest risk concerns individuals with P9DQ non-Asp 57 and both the charged P4 of DRB1 and P4 of DQB1, conferring a 80% prediction of susceptibility. Conversely, P9DQ Asp and neutral P4DR and P4DQ give the lowest risk with a predictive value of 5%. This model of risk susceptibility prediction fits remarkably well with the observed distribution in a worldwide study. It allows a better evaluation of the respective role of HLA-DR and -DQ molecules as a major component of susceptibility to IDDM. [ABSTRACT FROM AUTHOR]

Significant associations of HLA-DP alleles with chronic hepatitis B ( CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1*05:01 and *09:01, and three protective alleles, DPB1*02:01, *04:01, and *04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules. [ABSTRACT FROM AUTHOR]

The article presents a report documenting the additions and revisions to the nomenclature of HLA specificities. It states that a number of HLA gene fragments have been reported and named which includes HLA-T previously known as HLA-16 and HLA-V previously known as HLA-75. It further discusses the conditions for acceptance of new genes and allele sequences for official names. It also presents lists of the serological specificities or antigens associated with the alleles.

Allele and haplotype frequencies of the human leukocyte antigens (HLA) were studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy individuals. DNA-based HLA typing was performed using a microsphere-based array genotyping platform with sequence-specific oligonucleotide probes to distinguish HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C, 25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303, B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and DQB1*0501 were found with frequencies higher than 10%. Two representative haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B; A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101-Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501 for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated that the Vietnamese population shares HLA patterns with southern Chinese, Thai, Javanese and Micronesians, while it also retains unique characteristics. [ABSTRACT FROM AUTHOR]

The article reports that World Health Organization Nomenclature Committee for factor of the human leukocyte antigen (HLA) system has decided to publish an interim report listing updated tables of alleles including those assigned since the publication of the last full report in 2002 (1). There are required conditions for acceptance of new sequences for official names. Where a sequence is obtained from cDNA, or where polymerase chain reaction products are subcloned prior to sequencing, several clones should have been sequenced.

Presents an interim report of the World Health Organization Nomenclature Committee for Factors of the HLA System which lists updated tables of alleles. Naming of additional alleles; Serological specificities associated with alleles; Extension of HLA allele names; IMGT/HLA Sequence Database.

In order to determine highly immunogenic severe acute respiratory syndrome coronavirus (SARS-CoV) epitope peptides capable of inducing long-lasting immunity, we first screened immunoglobulin-G (IgG) antibodies reactive to 197 different overlapping 15-mers from the SARS-CoV proteins in the sera of three infected patients. Forty-two peptides among them were reactive to the sera from all three patients. Consequently, we tested for the reactivity of these 42 peptides to patients' sera (n = 45) at 6-month post-infection. The significantly higher levels of IgG antibodies specific to three (S791, M207 and N161) of 42 peptides were detectable in the post-infection sera from 23 (51%), 27 (60%) and 19 (42%) of 45 patients, respectively. These three peptides, recognized by their long-lasting immunity, may provide a better understanding of the immunogenicity of SARS-CoV. [ABSTRACT FROM AUTHOR]

Provides the nomenclature for factors of the human leukocyte antigen (HLA) system. Naming of additional genes within the HLA region; Naming of additional alleles; Renaming of alleles and removal of incorrect alleles; Extension of HLA allele names.

Two hundred and four unrelated Japanese patients with rheumatoid arthritis (RA) were typed for HLA by serological typing and DNA typing. The serological typing revealed that frequencies of HLA-A11, DR4, DR53 and DQ4 were increased and those of DR8 and DQ1 were decreased in the patients. The DNA typing has precisely defined the disease-associated HLA class II alleles; DRBl*0405, DQAl*03 and DQBl*0401 showed positive associations, while negative associations were found with DRBl*0803, DQAl*0103 and DQBl*0601. The risk for RA was found to be closely associated with particular amino acid sequences of DR-beta chain, including glycine residue at the 86th position in addition to those between 70 and 74, which are known to confer binding specificity and affinity to antigenic peptides. The observation that the frequency of HLA-A11 was increased in the DRBl*0405-positive patients suggested the interaction of these two alleles in the susceptibility to RA. On the other hand, the frequency of DPB1*0201 was increased in the DRBl*0405-negative patients and the frequency of HLA-A2 was increased in the DPBl*0201-positive patients, especially in the younger onset group. These findings suggested that the combination of HLA-A2 and DPBl*0201 may confer the susceptibility in the DRBl*0405-negative patients. Our results suggested the possibility that the susceptibility to RA is controlled by the interaction of HLA-A and DRBl genes or by that of HLA-A and DPBl genes in different patient subgroups. [ABSTRACT FROM AUTHOR]

Abstract: In order to understand the forces governing the evolution of the genetic diversity in the HLA-DP molecule, polymerase chain reaction (PCR)-based methods were used to characterize genetic variation at the DPA1 and DPB1 loci encoding this heterodimer on 2,807 chromosomes from 15 different populations including individuals of African, Asian, Amerindian, Indian and European origin. These ethnically diverse samples represent a variety of population substructures and include small, isolated populations as well as larger, presumably admixed populations. Ten DPA1 and 39 DPB1 alleles were identified and observed on 87 distinct DP haplotypes, 34 of which were found to be in significant positive linkage disequilibrium in at least one population. Some haplotypes were found in all ethnic groups while others were confined to a single ethnic group or population. Strong positive global linkage disequilibrium (Wn) between DPA1 and DPB1 was present in all 15 populations. The African populations displayed the lowest values of Wn whereas the Amerindian populations displayed near absolute disequilibrium. Analysis of the distribution of haplotypes using the normalized deviate of the Ewens-Watterson homozygosity statistic, F, suggests that DP haplotypes encoding the functional heterodimer are subject to much lower degrees of balancing selection than other loci within the HLA region. Finally, neighbor joining tree analyses demonstrate the power of haplotype diversity for inferring the relationships between the different populations. [ABSTRACT FROM AUTHOR]

Presents a nomenclature for factors of the HLA histocompatibility antigen system, released by the World Health Organization in 2000. Naming of new alleles; Serological specificities associated with alleles; Names for genes in the HLA region.

Abstract: A polymorphism in high-affinity receptor of TNF (TNFR2) gene, Met196Arg, was reported to be associated with systemic lupus ery-thematosus (SLE) in Japanese, whereas the association could not be found in Europeans at all and this represents an apparent discrepancy. The association, then, should be tested in other populations to clarify the possible involvement, if any, of the TNFR2 polymorphism in SLE or other related autoimmune diseases. The purposes of this study were to examine the TNFR2 polymorphism in Japanese patients with SLE and to investigate its association with other autoimmune diseases accompanied by vasculitis, mixed connective tissue disease, Buerger's disease, and Takayasu's arteritis. We found no association at all between the TNFR2 polymorphism and any autoimmune diseases including SLE in Japanese. [ABSTRACT FROM AUTHOR]

Polymorphisms in the 5-flanking region of the tumor necrosis factor (TNF)-α gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF-α-857T allele (designated as TNFP-D allele) or -863A/-1,031C allele (designated as TNFP-B allele) were significantly increased in the patients as compared with the controls. Since these TNF-α alleles are in linkage disequilibria with certain DRB1 and HLA-B alleles, two-locus analyses were carried out. The TNFP-D allele did not increase the risk in either the presence or absence of the DRB1∗0405 or HLA-B54 allele, while the DRB1∗0405 and HLA-B54 alleles per se could confer susceptibility in both the TNFP-D allele-positive and -negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1∗0405 and HLA-B54. Similarly, the TNFP-B allele did not show significant association with the disease in either the HLA-B61-positive or -negative population, while the HLA-B61 allele could significantly increase the risk in the TNFP-B allele-positive population. These data suggest that the associations of TNFP-D and -B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA-B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese. [ABSTRACT FROM AUTHOR]

The pathogenesis of histiocytic necrotizing lymphadenitis (HNL), which was reported first by Kikuchi et al. and Fujimoto et al. in 1972, is as yet unknown. HNL is frequently reported in Asian countries including Japan, however it is rare in Europe and North America. To elucidate whether the human leukocyte antigen (HLA) alleles and haplotypes are associated with HNL, we performed DNA typing of HLA class II genes (HLA-DR, -DQ, and -DP) in 86 patients with HNL and 525 unrelated healthy Japanese controls with polymerase chain reaction using sequence-specific oligonucleotide probes (PCR-SSOP). In this study, we found DPA1*01 and DPB1*0202 allele frequencies in HLA class II genes are significantly higher in HNL patients than in normal controls. It is known that the frequency of DPB1*0202 alleles is extremely low or absent in Caucasians (e.g., French 0.4%, Italian 0.8%) and Negroid (e.g., South African 0%, Hottentot 0%), but relatively frequent in Asians (e.g., Korean 9.9%, Japanese 4.5%). Previous reports have said the incidence of HNL is frequent in Asians but rare in other races. In light of this background, HLA class II genes of HNL and the incidence of HNL in Asian countries, including Japan, might have a positive relationship to DPA1*01 and DPB1*0202 allele. [ABSTRACT FROM AUTHOR]

Matching of human platelet alloantigen (HPA) systems 2–6 was retrospectively investigated in 715 unrelated bone marrow transplantations. Of the five HPA systems studied, HPA-5 mismatching was found to have a significant effect on the disease-free survival rate of recipients following transplantation in the HLA-A, -B, -C, and -DR allele-matched donor-recipient pairs. The effect of the HPA-5 mismatch was most significant in the recipient group possessing the HLA haplotype A*2402-B*5201, which is a highly frequent haplotype among the Japanese population. However, the probability of development of acute graft-versus-host disease (GVHD) was not increased significantly by the HPA-5 mismatching. These findings suggest that the HPA-5 mismatching decreases the recipient’s survival by a mechanism different from that in the case of mismatching of minor antigens found often in transplant recipients developing GVHD. [ABSTRACT FROM AUTHOR]

Presents a nomenclature for factors of the HLA system submitted by the WHO Nomenclature Committee at the ASHI congress in Vancouver, Canada. Names of the genes; Revision of the naming policy; Serological specificities of the genes.

Presents a nomenclature for factors of the HLA system submitted by the WHO Nomenclature Committee at the ASHI congress in Vancouver, Canada. Names of the genes; Revision of the naming policy; Serological specificities of the genes.

Abstract: The association of various HLA class II loci with Crohn's disease (CD) and ulcerative colitis (UC) has yet to be fully elucidated. To determine whether there is an association of HLA class II genes (DR, DQ and DP alleles) with inflammatory bowel disease (IBD), HLA class II genes for polymorphisms were analyzed at the DNA level in 111 patients with CD, 81 with UC and 525 healthy controls by the polymerase chain reaction-sequence specific oligonucleotide probe method. Allele and haplotype frequencies were compared between these populations. Results were as follows: 1) the presence of DQB1∗0402 (RRequals3.90, P[subc]equals0.0001) was positively associated with CD; 2) the presence of DRB1∗1502 (RRequals4.51, P[subc]<1×10[sup−8]), DRB5∗0102 (RRequals4.70, P[subc]<1time;10[sub−8]), DQA1∗0103 (RRequals3.72, P[subc] equals1×10[sup&minus5] ), DQB1&lowast06011 (RRequals3.78, P[subc] equals1×10[sub&minus5]), DPA1∗0201 (RRequals3.23, P[subc]&equals;0.0001) and DPB1∗0901 (RRequals4.83, P[subc]<1×10[sup−8]) was positively associated and that of DRB4&lowast0101 (RRequals0.20, P[subc]<1%times;10[sup&minus8]) and DQA1&lowast0302 (RRequals0.34, P[subc]equals0.001) negatively associated with UC; 3) haplotype analysis showed a positive association between the presence of DRB1∗0410-DQA1∗0302-DQB1∗0402 and DRB1∗ 0802-DQA1∗0401-DQB1∗0402 with CD, and a negative association between the presence of DRB1∗1502-DQA1∗0103- DQB1&lowast06011 and CD, there was no association of DRB1∗08032- DQA1∗0103-DQB1∗06011 with CD; and 4) in UC, a positive association with the presence of DRB1∗1502-DQA1∗0103- DQB1∗06011 was found, but DRB1∗08032-DQA1∗0103- DQB1∗06011 was not associated with it. In conclusion, in CD in the Japanese population, HLA-linked disease susceptibility... [ABSTRACT FROM AUTHOR]

Presents the table of contents of the volume 62 of the 2003 issue of the 'Tissue Antigens' journal.