A reliable and safe T cell repertoire based on low-affinity T cell receptors.
Antigens are presented to T cells as short peptides bound to MHC molecules on the surface of body cells. The binding between MHC/peptides and T cell receptors (TCRs) has a low affinity and is highly degenerate. Nevertheless, TCR-MHC/peptide recognition results in T cell activation of high specificity. Moreover, the immune system is able to mount a cellular response when only a small fraction of the MHC molecules on an antigen-presenting cell is occupied by foreign peptides, while autoimmunity remains relatively rare. We consider how to reconcile these seemingly contradictory facts using a quantitative model of TCR signalling and T cell activation. Taking into account the statistics of TCR recognition and antigen presentation, we show that thymic selection can produce a working T cell repertoire which will produce safe and effective responses, that is, recognizes foreign antigen presented at physiological levels while tolerating self. We introduce "activation curves" as a useful tool to study the repertoire's statistical activation properties.
Van Den Berg
H A
HA
Mathematics Institute, University of Warwick, Coventry CV4 7AL, UK.
Rand
D A
DA
Burroughs
N J
NJ
D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000378:metabolism*
D011948:Receptors, Antigen, T-Cell