GERMLINE TCR-A RESTRICTION OF IMMUNOGLOBULIN-E RESPONSES TO ALLERGEN

Immunoglobulin E responses to known environmental antigens (allergens) may serve as a general model to investigate germline genetic restrict ion of the immune response. We have previously shown genetic linkage b etween IgE responses to major allergens and the T-cell receptor (TCR) A/D locus, but not to TCR-B, implying that elements in TCR A/D restric t the ability to react to specific antigens. We now show, in two sets of subjects from the same population, a strong allelic association bet ween a VA8.1 polymorphism (VA8.12) and reactivity to Der p II, a majo r antigenic component of the house dust mite Dermatophagoides pteronys sinus. Association was also seen between Der p II IgE titres and HLA-D RB11501 alleles. Reactivity to Der p II was confined to subjects who were positive for VA8.12 and HLA DRB1*1501, demonstrating germline HL A-DR and TCR-A interaction in restricting the response to exogenous an tigen.