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 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.
Salzmann
M
M
Basel Institute of Immunology, Switzerland.
Bachmann
M F
MF
D000818:Animals; D017951:Antigen Presentation; D019281:Dimerization; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell