Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner.

ABSTRACT: Presentation of peptides by class I MHC proteins underlies T cell immune responses to pathogens and cancer. The association between peptide binding affinity and immunogenicity has led to the engineering of modified peptides with improved MHC binding, with the hope that these peptides would be useful for eliciting cross-reactive immune responses directed toward their weak binding, unmodified counterparts. Increasing evidence, however, indicates that T cell receptors (TCRs) can perceive such anchor-modified peptides differently than wild-type (WT) peptides, although the scope of discrimination is unclear. We show here that even modifications at primary anchors that have no discernible structural impact can lead to substantially stronger or weaker T cell recognition depending on the TCR. Surp

SUBMITTER: Smith AR 

PROVIDER: S-EPMC7848747 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature