Genetic control of immune response and disease susceptibility by the HLA-DQ gene.

The particular alleles of the HLA-DQ locus may control the low immune response to natural antigens by a dominant genetic trait through the immune suppression mediated by CD8+ suppressor T cells. The suppressor T cells may be activated by DQ-restricted and antigen-specific CD4+ suppressor/inducer T cells, because (1) a statistically significant association and linkage between low immune responsiveness to the natural antigens and the HLA-DQ gene were observed; (2) antigen-specific CD4+ T cells restricted by the DQ molecules encoded for by the HLA-DQ allele associated with low responsiveness were evidenced in many low responders; and (3) anti-HLA-DQ mAb restored the immune response to natural antigens, in some low responders. This HLA-DQ-controlled polymorphism of immune response to the natural antigens may account for the association between HLA-DQ alleles and organ-specific autoimmune diseases.