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 phenotypic trait to analyse genetic predisposition in trichosanthin (Tk)-induced immuno-suppression. Tk is a natural protein antigen with 247 amino acid residues. Based on DNA typing for DR, DQ, DP and TAP genes, data in this paper indicate that only DQ genes were primarily involved and that the alleles DQA10501 and DQB10201 were strongly associated with the M+ phenotype in cis (on DR3 haplotype) or trans (on DR5/DR7 heterozygotes) complementation. This is consistent with our observation that only the DQ-positive cells were capable of expanding after being co-cultured with Tk for 96 h. Two points of interest were noted. (1) The susceptible haplotype DRB10301-DQA10501-DQB10201 showed an association with the M+ phenotype only if combined with DRB104-, DRB108-, or DRB109-related haplotypes. When co-presented with DRB111-, DRB115-, DRB107-related haplotypes, however, no cis complementation could be detected. A detailed analysis of the association patterns indicated that the DQB1 locus of the non-susceptible haplotypes was the main factor for up- or down-modulation. (2) For M+ phenotype-related trans complementation in Tk-induced suppression, it was found that not only DQA10501-DQB10201 (DR5/7) alleles, but also associated DQA10301-DQB10201 (DR4/7, 9/7) alleles, were involved. The allele DQB10201 was not associated with the DQA1 alleles in DRB101-, DRB115-, DRB113-, DRB107-related haplotypes. The results obtained indicate that there are some additional genetic factors involved in the functional expression of cis and trans complementation of DQA1 and DQB1 genes, among which the DQ alleles play a critical role as self-regulators.