CARBOHYDRATE-DEPENDENT, HLA CLASS II-RESTRICTED, HUMAN T-CELL RESPONSE TO THE BEE VENOM ALLERGEN PHOSPHOLIPASE-A2 IN ALLERGIC PATIENTS

The T cell-independent antibody response to polysaccharide antigen (Ag ) is believed to result from their inability to bind major histocompat ibility complex (MHC) restriction elements. However, recent studies us ing glycosylated analogues of known immunogenic peptides revealed that glycopeptides can interact with MHC molecules and are able to elicit specific T cell responses in experimental animals. This raises questio ns about the possible role which carbohydrates can play in T cell resp onses following natural exposure to glycoprotein antigens. Analyzing t he fine specificity of the human T cell response against the major bee venom allergen phospholipase A2 (PLA), a 16-20-kDa protein glycosylat ed at a single site (Asn(13)), we have identified several T cell clone s which proliferate in response to the glycoprotein but not to its non -glycosylated variants. Neither the carbohydrate moiety alone nor the combination of carbohydrate and nonglycosylated protein could substitu te for the intact glycoprotein. Antibody directed against the carbohyd rate moiety inhibited Ag-induced proliferation of these clones whereas control clones with known peptide specificity were not affected, prov iding additional evidence for the involvement of carbohydrates in T ce ll recognition. Moreover, peripheral blood mononuclear cells of two in dividuals from whom glycosylation-dependent T cell clones have been is olated showed significantly higher proliferation in response to glycos ylated compared to non-glycosylated Ag, suggesting that glycosylation can contribute in some cases extensively to the immunogenicity of a gl ycoprotein Ag. Thus, this report shows that glycosylation-dependent Ag recognition by T cells can also occur following natural exposure to a glycoprotein.