The role of T cell receptor dimerization for T cell antagonism and T cell specificity

Abstract

T cell responses are highly specific and T cell receptors (TCRs) can recognise 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 peptides exhibiting mutations at the TCR-MHC/peptide contact site stimulate only a fraction of T cell responses (partial agonists) or may even inhibit T cell activation by full agonists (antagonist). The present study analyses mathematically the role of TCR-dimerization for T cell antagonism and T cell specificity in general. It demonstrates that T cell antagonists can effectively inhibit TCR-dimerization and that this mechanism can sufficiently explain all aspects of T cell antagonism. The kinetic model of T cell activation proposes that increasing the time 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.