Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro.

ABSTRACT: T cell receptors (TCRs) bind to peptide-major histocompatibility complex (pMHC) with low affinity (K_d ∼ μM), which is generally assumed to facilitate cross-reactive TCR "scanning" of ligands. To understand the relationship between TCR/pMHC affinity and cross-reactivity, we sought to engineer an additional weak interaction, termed "velcro," between the TCR and pMHC to probe the specificities of TCRs at relatively low and high affinities. This additional interaction was generated through an eight-amino acid peptide library covalently linked to the N terminus of the MHC-bound peptide. Velcro was selected through an affinity-based isolation and was subsequently shown to enhance the cognate TCR/pMHC affinity in a peptide-dependent manner by ∼10-fold. This was sufficient to con

SUBMITTER: Gee MH 

PROVIDER: S-EPMC6077720 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature