T-CELL RECOGNITION OF HAPTENS, A MOLECULAR VIEW

Our review attempts to summarize the present knowledge on how T lympho cytes recognize chemically modified autologous cells. Concerning the b road spectrum of chemically and drug-induced allergic and autoimmune d iseases, the molecular mechanisms of hapten recognition by T cells are clearly of more than academic interest. The past few years revealed t hat in contrast to the expectations of many researchers, major histoco mpatibility complex (MHC)restricted, hapten-specific T cell receptors in their majority do not react to covalently modified MHC molecules, b ut to haptenized peptides associated with the MHC peptide-binding groo ve. This finding allowed the introduction of synthetic hapten-peptide conjugates, the MHC specificity of which may be predetermined by allel e-specific peptide sequence motifs. Thus, it has now become feasible t o selectively hapten-modify defined sets of MHC molecules on living ce lls, and to study their immunological properties. In that way two majo r types of hapten-specific T cell receptors were identified: one react ing to hapten without caring for the chemical composition of the carri er peptide, and the other contacting hapten and peptide by two apparen tly independent contact sites. The consequences of these findings for hapten-specific allergies and autoimmunities, but also for our molecul ar understanding of antigen recognition by T cells are discussed.