An Engineered Switch in T Cell Receptor Specificity Leads to an Unusual but Functional Binding Geometry.

ABSTRACT: Utilizing a diverse binding site, T cell receptors (TCRs) specifically recognize a composite ligand comprised of a foreign peptide and a major histocompatibility complex protein (MHC). To help understand the determinants of TCR specificity, we studied a parental and engineered receptor whose peptide specificity had been switched via molecular evolution. Altered specificity was associated with a significant change in TCR-binding geometry, but this did not impact the ability of the TCR to signal in an antigen-specific manner. The determinants of binding and specificity were distributed among contact and non-contact residues in germline and hypervariable loops, and included disruption of key TCR-MHC interactions that bias αβ TCRs toward particular binding modes. Sequence-fitness landscapes id

SUBMITTER: Harris DT 

PROVIDER: S-EPMC4938795 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature