|Title||Geometrical characterization of T cell receptor binding modes reveals class-specific binding to maximize access to antigen.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Singh, NK, Abualrous, ET, Ayres, CM, Noé, F, Gowthaman, R, Pierce, BG, Baker, BM|
|Date Published||2019 Oct 07|
Recognition of antigenic peptides bound to major histocompatibility complex (MHC) proteins by αβ T cell receptors (TCRs) is a hallmark of T cell mediated immunity. Recent data suggests that variations in TCR binding geometry may influence T cell signaling, which could help explain outliers in relationships between physical parameters such as TCR-pMHC binding affinity and T cell function. Traditionally, TCR binding geometry has been described with simple descriptors such as the crossing angle, which quantifies what has become known as the TCR's diagonal binding mode. However, these descriptors often fail to reveal distinctions in binding geometry that are apparent through visual inspection. To provide a framework for better relating TCR structure to T cell function, we developed a comprehensive system for quantifying the geometries of how TCRs bind peptide/MHC complexes. We show that our system can discern differences not clearly revealed by the more common methods. As an example of its potential to impact biology, we used it to reveal differences in how TCRs bind class I and class II peptide/MHC complexes, which we show allow the TCR to maximize access to and "read out" the peptide antigen. We anticipate our system will be of use in not only exploring these and other details of TCR-peptide/MHC binding interactions, but also addressing long-held questions about how TCR binding geometry relates to T cell function, as well as modeling structural properties of class I and class II TCR-peptide/MHC complexes from sequence information. This article is protected by copyright. All rights reserved.