High-affinity CD8 variants enhance the sensitivity of pMHCI antigen recognition via low-affinity TCRs.

ABSTRACT: CD8⁺ T cell-mediated recognition of peptide-major histocompatibility complex class I (pMHCI) molecules involves cooperative binding of the T cell receptor (TCR), which confers antigen specificity, and the CD8 coreceptor, which stabilizes the TCR/pMHCI complex. Earlier work has shown that the sensitivity of antigen recognition can be regulated in vitro by altering the strength of the pMHCI/CD8 interaction. Here, we characterized two CD8 variants with moderately enhanced affinities for pMHCI, aiming to boost antigen sensitivity without inducing non-specific activation. Expression of these CD8 variants in model systems preferentially enhanced pMHCI antigen recognition in the context of low-affinity TCRs. A similar effect was observed using primary CD4⁺ T cells transduced

SUBMITTER: Knezevic L 

PROVIDER: S-EPMC10432799 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature