T cell recognition of haptens, a molecular view

Our review attempts to summarize the present knowledge on how T lymphocytes recognize chemically modified autologous cells. Concerning the broad spectrum of chemically and drug-induced allergic and autoimmune diseases, the molecular mechanisms of hapten recognition by T cells are clearly of more than academic interest. The past few years revealed that in contrast to the expectations of many researchers, major histocompatibility complex (MHC)-restricted hapten-specific T cell receptors in their majority do not react to covalently modified MHC molecules, but to haptenized peptides associated with the MHC peptide-binding groove. This finding allowed the introduction of synthetic hapten-peptide conjugates, the MHC specificity of which may be predetermined by allele-specific peptide sequence motifs. Thus, it has now become feasible to selectively hapten-modify defined sets of MHC molecules on living cells, and to study their immunological properties. In that way two major types of hapten-specific T cell receptors were identified: one reacting to hapten without caring for the chemical composition of the carrier peptide, and the other contacting hapten and peptide by two apparently independent contact sites. The consequences of these findings for hapten-specific allergies and autoimmunities, but also for our molecular understanding of antigen recognition by T cells are discussed.