The discriminatory power of the T cell receptor

<jats:title>Abstract</jats:title><jats:p>T cells use their T-cell receptors (TCRs) to discriminate between lower-affinity self and higher-affinity non-self pMHC antigens. The strength of this discrimination and the mechanisms that produce it remain controversial. Although a large number of mouse and human TCRs have now been characterised, they have not been used to precisely quantitate discrimination. Here, we systematically quantify the discrimination of TCRs using a discrimination power (<jats:italic>α</jats:italic>). Early influential studies on three mouse TCRs suggested that discrimination was nearly perfect (<jats:italic>α</jats:italic> ~ 9.0). In striking contrast, our analysis of published data on other mouse and human TCRs, and more recent data on the original mouse TCRs, produced significantly lower discrimination (<jats:italic>α</jats:italic> = 2.0). Although not perfect, the discriminatory power of TCR was greater than that of conventional receptors such as cytokine receptors, GPCRs, RTKs, and CARs (<jats:italic>α</jats:italic> ≤ 1). The revised discriminatory power of the TCR is readily explained by a kinetic proofreading mechanisms, and accounts for the ability of low affinity self-antigens to stimulate autoimmune and anti-tumour T cell responses.</jats:p>