Cis-trans complementation of DQA1-DQB1 genes are modulated by DQ alleles: an immunogenetics analysis of DQ association with the down-regulatory function of CD8 cells in trichosanthin-induced immunosuppression

The initiation of a CD8 cell-mediated pathway (M+) was adopted as a phenoty pic trait to analyse genetic predisposition in trichosanthin (Tk)-induced i mmunosuppression. Tk is a natural protein antigen with 247 amino acid resid ues. Based on DNA typing for DR, DQ, DP and TAP genes, data in this paper i ndicate that only DQ genes were primarily involved and that the alleles DQA 1*0501 and DQB1*0201 were strongly associated with the M+ phenotype in cis (on DR3 haplotype) or trans (on DR5/DR7 heterozygotes) complementation. Thi s is consistent with our observation that only the DQ-positive cells were c apable of expanding after being co-cultured with Tk for 96 h. Two points of interest were noted. (1) The susceptible haplotype DRB1*0301-DQA1*0501-DQB 1*0201 showed an association with the M+ phenotype only if combined with DR B1*04-, DRB1*08-, or DRB1*09-related haplotypes. When co-presented with DRB 1*11-, DRB1*15-, DRB1*07-related haplotypes, however, no cis complementatio n could be detected. A detailed analysis of the association patterns indica ted that the DQB1 locus of the non-susceptible haplotypes was the main fact or for up- or down-modulation. (2) For M+ phenotype-related trans complemen tation in Tk-induced suppression, it was found that not only DQA1*0501-DQB1 *0201 (DR5/7) alleles, but also associated DQA1*0301-DQB1*0201 (DR4/7, 9/7) alleles, were involved. The allele DQB1*0201 was not associated with the D QA1 alleles in DRB1*01-, DRB1*15-, DRB1*13-, DRB1*07-related haplotypes. Th e results obtained indicate that there are some additional genetic factors involved in the functional expression of cis and trans complementation of D QA1 and DQB1 genes, among which the DQ alleles play a critical role as self -regulators.