摘要:

In order to further clarify the diversity of the HLA‐B15 antigens and the correspondence of serological types with alleles in Asians, we screened various B15 serological splits by means of a polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) method. Subsequently, the genes encoding various B15 variants were sequenced. Two novel alleles, B*1528 and B*1529, were identified: the nucleotide sequence of the former contained a single‐base substitution at position 263 in exon 2 as compared to that of the B*1501 allele, which results in an amino acid change at position 64 in the α1 domain, and the nucleotide sequence of the latter differs from that of B*1518 by a single‐base substitution at position 272 of exon 2 which results in an amino acid change at position 67 of the α1 domain. One new allele, B*1521, described recently in Australian Aborigines was also identified in Asians in the present study. Moreover, the results of sequencing demonstrated that Asian HLA‐B62, B70, and B77 antigens are encoded by B*1501, B*1518, and B*1513, respectively. Two splits of B75 antigens, B75V (TS‐1) and B15N, which have been proposed to exist in the Japanese population were encoded by B*1511 and B*1502, respectively. Most of the B15 alleles detected in the present study showed positive associations with other locus antigens. Especially, B*1502 was strongly associated with Cw8, while B*1521 was strongly associated w

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02553.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The aim of this study was to determine the association between childhood insulin‐dependent diabetes mellitus (IDDM) and HLA‐DR4 subtypes and to test in a population‐based investigation whether the DR4 association has an effect independent to that of DQ. First, HLA genotyping identified DR4 in 337/425 (79%) patients and 148/367 (40%) controls (Odds Ratio 5.67; p<0.01). Second, a total of 14 DR4 subtypes were detected by PCR and sequence specific oligo probes. Only two DR4 subtypes, DRB1*0401 (62% patients and 25% controls; OR 4.95, p<0.01) and *0404 (16% patients and 10% controls; OR 1.67, p<0.05) were however positively associated with the disease. These two subtypes were positively associated only when linked to DQB1*0302‐DQA1*0301 (DQ8) (56% patients and 14% controls; OR 7.69, p<0.01; 15% patients and 10% controls; OR 1.55, p<0.05, respectively). When DRB1*0401 was linked to DQB1*0301‐DQA1*0301 (DQ7) (6% patients and 11% controls; OR 0.52, pDRB1*0404 and the association of DRB1*0401 has a significant effect in DQ8 positive IDDM patients. We conclude that the DR4 association with IDDM is secondary to DQ by linkage disequilibrium, which support the role of HLA‐DQ as a primary genetic risk fa

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02554.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

We describe here a rapid polymerase chain reaction (PCR)‐based method for the identification of HLA‐DRB1*0401‐*0412 alleles. The method is based on the generation of specific DNA heteroduplex patterns between PCR products derived from selective group‐specific amplification of the various DRB1*04 alleles and PCR products derived from two synthetic DNA heteroduplex generator (DHG) molecules following non‐denaturing polyacrylamide minigel electrophoresis. One DHG was designed to detect DRB1*0401, *0405, *0407, *0408, and *0409 alleles, whilst the other was designed to detect DRB1*0402, *0403, *0404, *0406, *0410, *0411, and *0412 alleles. Characteristic heteroduplex patterns were obtained for all DRB1*04 alleles tested both in homozygous and heterozygous situations. Both DHG and PCR‐SSP (sequence‐specific primer) typing were performed on 41 DRB1*04 positive DNAs from Singaporean Chinese blood donors and complete concordance in results was obtained. HLA‐DRB1*0403, *0405, and *0406 were found to account for 95% of the DRB1*04 alleles in the population studied. The DHG technique described is technically simple and rapid since it essentially involves only two PCR amplifications per individual subtyping. The technique is particularly useful for resolving DRB1*04 combinations which are indistinguishable by PCR‐SSO (sequence‐specific oligonucleotide) o

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02555.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

HLA‐DPB1 genotyping of 241 individuals from an African Bantu‐speaking population in central Cameroon using sequence‐specific oligonucleotide probes identified five individuals with novel probe hybridization patterns. DNA sequence analysis of the second exon of the DPB1 alleles from these five individuals identified three new alleles, *6001, *6101N, and *6201. DPB1*6001, found in two individuals, contains a single nucleotide change that results in a polar amino acid, asparagine, at residue 65; this position in the β1 domain is occupied by a nonpolar amino acid in all other reported DPB1 alleles. DPB1*6101N, found in one individual, contains a single base mutation that results in a premature termination codon at position 67. DPB1*6201, found in two individuals, is characterized by the apparent motif shuffling that has been hypothesized to be responsible for the majority of DPB1 sequence polymorphism. These new sequences shed additional light on the potential mechanisms by which allelic diversity is generated at the HLA‐DP

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02556.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

HLA‐DP molecules function as restriction elements in the presentation of foreign antigens to T cells by antigen presenting cells and certain HLA‐DP molecules confer susceptibility to autoimmune disease. Because HLA molecules play an essential role in thymic selection and elimination of autoreactive T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA‐DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA‐DP molecules. The expression of HLA‐DP molecules was comparable to or higher than the expression of HLA‐DQ but lower than that of HLA‐DR. Upon IFN‐γ treatment, HLA‐DP expression was strongly upregulated. Since HLA‐DQ and DR expression was upregulated in parallel, the hierarchy between MHC class II isotypes remained unchanged following interferon treatment. TEC elicited significant proliferation of HLA‐DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN‐γ treatment strongly upregulated the HLA‐DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels of

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02557.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Fifty pregnancy alloantisera directed towards HLA‐A23 and/or A24 antigens were investigated serologically in titration studies against the three sequenced HLA‐A9 specificities, A23 (A*2301), A24 (A*2402) and A2403 (A*2403). The reaction patterns of the antisera fell into five categories which allowed the three HLA‐A9 specificities to be easily differentiated. Based on the various titre cytotoxicity scores of the antisera five possible antibody specificities were defined: anti‐A23; ‐A24; ‐A23/24; ‐A24/2403 and anti‐A23/24/2403. One antiserum crossreacted with HLA‐A1 and A24. Inspection of the amino acid sequences of 136 HLA‐A, B and C molecules allowed the prediction of five unique epitopes corresponding to these antibody specificities, a possible epitope unique to A2403 and confirmation of a likely epitope shared by A1 and A24. These, together with the previously suggested epitopes HLA‐A9/ A2/A28 and A1/A23/A24 together with the presence of Bw4 on the three HLA‐A9 antigens suggests that the HLA‐A9 family of antigens is characterized by a minimum of nine serolog

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02558.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Children with perinatally‐acquired HIV‐1 infection were studied to determine if major histocompatibility complex (MHC) genes are involved in progression to pediatric AIDS. Molecular genetic techniques were used to genotype loci in the class II region (DRB1, DQA1, DQB1, DPA1, DPB1, LMP2 and LMP7). HIV‐infected children were classified by clinical manifestations and degree of immunosuppression using age‐specific CD4 T‐lymphocyte counts at enrollment. Alleles at the DPB1 and DQB1 loci showed independent and opposite associations; DPB1*0301 showed a trend toward protection while DQB1*0201 appeared to be a risk factor for developing severe immunosuppression and severe clinical outcomes. Presence of DQB1*0201 conferred a greater than 10‐fold increased odds of having severe clinical manifestations and a 2.8‐fold increased odds of severe immunosuppression. Presence of DPB1*0301 was associated with a greater than 8‐fold decreased odds of severe immunosuppression and severe clinical manifestations. These results support host genetic influences on HIV‐1 out

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02559.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Up to now 19 allelic sequences of the rhesus monkeyDQB1locus have been published. Referring to these sequences, we have developed a typing protocol forMamu‐DQB1alleles which was verified by additional cloning, sequence analysis and segregation studies. The protocol is based on the amplification of the second exon with only one specific primer pair followed by the digestion of the PCR products with up to 10 different restriction endonucleases. The alleles can be identified in homozyous and heterozygous combinations since most amplified second exon sequences give unique band patterns after digestion with at least one of the selected restriction endonucleases. By the use of this protocol we analyzed DNA‐samples from 182 rhesus monkeys. Among these samples two novelMamu‐DQB1alleles were detected, subsequently cloned and their nucleic sequence determined. Since we typed four complete breeding groups consisting of two generations we were able to identify several DQ haplotypes by segregation analysis using the previously developed typing protocol fo

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02560.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

A novel HLA‐Cw*15, B7 haplotype has been found in Caucasians. Molecular cloning studies demonstrate that this haplotype is constituted by the new alleles Cw*15052 and B*0706, which seem to be intermediate steps in the diversification of their respective allelic families. A pathway for the evolution of Cw*15 alleles is propose

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02561.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Transracial analysis is one method for distinguishing primary associations between insulin‐dependent diabetes mellitus (IDDM) and HLA II alleles from those related to linkage disequilibrium. Black people have different DR‐DQ relationships from other races and are a useful group to investigate HLA‐D regions associated with IDDM. In this study, we compared the frequencies of HLA‐DQA1 and DQB1 alleles in Senegalese IDDM and control subjects. DQA1*0301 was positively associated with insulin‐dependent diabetes mellitus (p<10‐9, OR 5.21), as were DQB1*0201 and *0302 (p<10‐7OR=3.55, p<10‐3OR=3.20, respectively). The positive associations with DQA1*0301, DQB1*0201 and DQB1*0302 are consistent with all racial groups investigated. However, taken together, the data in Senegalese population show that susceptibility and resistance to IDDM are associated both with particular haplotypes and DQA1‐

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1996.tb02562.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY