Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites.
Insulin-dependent diabetes mellitus (IDDM) susceptibility is associated with the DR4-DQw4 haplotype in Japanese and the DR4-DQw8/-Drw8-DQw4 genotype (among others) in whites. We investigated whether these Japanese and white individuals encode the same or a similar DQ alpha beta heterodimer, which may be an IDDM-susceptibility molecule in both populations. First, we carried out genomic DQA1 and DQB1 typing with sequence-specific oligonucleotide probes. The results revealed that Japanese DR4-DQw4 and white DR4-DQw8/DRw8-DQw4 IDDM patients carried the DQA1*0301 allele and the DQB1*0401 or DQB1*0402 allele, either in the cis (Japanese DR4-DQw4 individuals) or trans (white DR4-DQw8/DRw8-DQw4 individuals) position. Because the DQB1*0401 and DQB1*0402 alleles differ only at residue 23, these DQB1 genes are very similar. We next tested cells from these individuals with a particular DQ-specific T-lymphocyte clone, HH58. The clone was only restimulated with cells from Japanese individuals who carried the DQA1*0301 and DQB1*0401 alleles in the cis position or white individuals who carried the DQA1*0301 and DQB1*0402 alleles in the trans position. Thus, particular cis- or trans-encoded DQ alpha beta heterodimers, which in both cases are recognized by T lymphocytes, may confer susceptibility to IDDM in both ethnic groups.
Rønningen
K S
KS
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
Gjertsen
H A
HA
Iwe
T
T
Spurkland
A
A
Hansen
T
T
Thorsby
E
E
D000483:Alleles; D044466:Asian People; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000208:ethnology; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D009664:Norway; D013601:T-Lymphocytes / Q000276:immunology; D044465:White People
D006683:HLA-DQ Antigens; C060029:HLA-DQ4 antigen; C109756:HLA-DQ8 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen; C041559:HLA-DR8 antigen; D046911:Macromolecular Substances