A Reliable and Safe T Cell Repertoire based on Low-affinity T Cell Receptors

✍ Scribed by H.A. VAN DEN BERG; D.A. RAND; N.J. BURROUGHS

• Publisher: Elsevier Science
• Year: 2001
• Tongue: English
• Weight: 505 KB
• Volume: 209
• Category: Article
• ISSN: 0022-5193
• DOI: 10.1006/jtbi.2001.2281

✦ Synopsis

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.