Molecular and cellular studies of human immune responsiveness to the short ragweed allergen, Amb a V

Specific immune responsiveness to the Amb a V allergen (from Ambrosia artemisiifolia, short ragweed pollen) is significantly associated with the Class II specificities, human leucocyte antigen (HLA)-DR2 and Dw2 determined by serological and MLR typing ("DR2.2"). Similarly, responsiveness to homologous Amb t V and Amb p V allergens is associated with DR2.2. We examined the deoxyribonucleic acid (DNA) sequences of HLA-DRB1, DRB5, DQB1 and DQA1 genes associated with Amb a V responsiveness using a combination of polymerase chain reaction (PCR), dot-blot and DNA sequencing methodologies. Our focus was on the highly polymorphic regions within the second-exon gene segments that are believed to encode antigen (Ag)-binding portions of the respective Class II molecules. Analysis of three patients having unusual sequence combinations of HLA-D gene sequences implicate an HLA-DR molecule (either DR alpha beta I 2.2 or DR alpha beta V 2.2), rather than a DQ Class II molecule, as the major Amb a V immune response (Ir) gene product. Our studies suggest that this DR2.2 molecule is usually a necessary, and almost always a sufficient, requirement for high immunoglobulin E and G (IgE) and (IgG) antibody responsiveness in ragweed-allergic individuals. From an atopic DR2.2+ subject, we isolated three Amb a V-specific T-cell clones. Analysis revealed these clones to be DR-restricted, supporting the conclusion that the Amb a V-Ir gene is a DR and not a DQ molecule. The DR beta I polypeptide of DR2.2 and 2.12 was implicated in Ag presentation, since monoclonal antibody (MoAb) Hu30 (antibody specific for DR beta I) blocked T-cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)