TCRs with high affinity for foreign pMHC show self-reactivity.
T cells with high-affinity T cell receptors (TCRs) for a foreign peptide-major histocompatibility complex (pMHC) appear to be negatively selected, even though they have never seen the foreign antigen. To examine how this process operates, we used in vitro yeast display to isolate high-affinity TCRs from the T cell clone 2C. The TCRs showed fast on-rates, which were consistent with reduced CDR (complementarity determining region) flexibility, and cross-reactivity with other cognate pMHCs. T cell hybridomas transfected with a high-affinity TCR were stimulated by endogenous self-pMHC, which suggested that T cells bearing the TCR would be negatively selected. The immune system appears to maintain a repertoire of flexible, low-affinity TCRs at the expense of more effective high-affinity TCRs.
Holler
Phillip D
PD
Department of Biochemistry, University of Illinois, Urbana, IL 61801, USA.
Chlewicki
Lukasz K
LK
Kranz
David M
DM
D000818:Animals; D001324:Autoantigens; D022801:Complementarity Determining Regions; D003429:Cross Reactions; D006825:Hybridomas / Q000276:immunology; D066298:In Vitro Techniques; D007700:Kinetics; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D008958:Models, Molecular; D019151:Peptide Library; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D013816:Thermodynamics
D001324:Autoantigens; D022801:Complementarity Determining Regions; D046911:Macromolecular Substances; D019151:Peptide Library; D011948:Receptors, Antigen, T-Cell