Canonical T cell receptor docking on peptide–MHC is essential for T cell signaling
Pirooz Zareie, Christopher Szeto, Carine Farenc, Sachith D. Gunasinghe, Elizabeth Motunrayo Kolawole, Angela Nguyen, Chantelle Blyth, Xavier Y.X. Sng, Jasmine Li, Claerwen M. Jones, Alex J. Fulcher, Jesica R. Jacobs, Qianru Wei, Łukasz Wojciech, Jan Petersen, Nicholas R. J. Gascoigne, Brian D. Evavold, Katharina Gaus, Stéphanie Gras, Jamie Rossjohn, Nicole L. La Gruta
Abstract
Making sense of TCR–pMHC topology Most T cells use a T cell receptor (TCR) that recognizes major histocompatibility complex molecules bound to peptides (pMHCs) derived from both self- and foreign antigens. Although there is great variability in the interface because of the diversity of both partners, this interaction displays a canonical docking topology for reasons that remain contested. Zareie et al. tested an assortment of both canonical and reversed-polarity TCRs that were all specific for the same cognate pMHC-I bearing a peptide derived from influenza A virus (IAV) (see the Perspective by Horkova and Stepanek). The authors determined that docking topology was the primary driver of in vivo T cell activation and recruitment when mice were infected with IAV. The canonical topology was required for the formation of a functional signaling complex, suggesting that T cell signaling constraints dictate how TCR and pMHC meet. Science , abe9124, this issue p. eabe9124 ; see also abj2937, p. 1038