THE ROLE OF T-CELL RECEPTOR DIMERIZATION FOR T-CELL ANTAGONISM AND T-CELL SPECIFICITY

T cell responses are highly specific and T cell receptors (TCRs) can r ecognise subtle differences in major histocompatibility complex (MHC)- peptide complexes. While nominal peptide antigens usually act as full agonists that trigger the whole spectrum of T cell responses, some pep tides exhibiting mutations at the TCR-MHC/peptide contact site stimula te only a fraction of T cell responses (partial agonists) or may even inhibit T cell activation by full agonists (antagonist). The present s tudy analyses mathematically the role of TCR-dimerization for T cell a ntagonism and T cell specificity in general. It demonstrates that T ce ll antagonists can effectively inhibit TCR-dimerization and that this mechanism can sufficiently explain all aspects of T cell antagonism. T he kinetic model of T cell activation proposes that increasing the tim e required for effective TCR-signaling is the most effective mechanism to increase the discriminatory capacity of TCRs. Our results indicate that TCR-oligomerization is an alternative and efficient mechanism to ensure T cell specificity. (C) 1998 Elsevier Science Ltd. All rights reserved.