Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

<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>

Original publication

DOI

10.1101/2020.11.16.384495

Type

Journal article

Publisher

Cold Spring Harbor Laboratory

Publication Date

17/11/2020