Proteins. 2022 Apr 10. doi: 10.1002/prot.26343. Online ahead of print.
ABSTRACT
The startling diversity in αβ T cell receptor (TCR) sequences and structures complicates molecular-level analyses of the specificity and sensitivity determining T cell immunogenicity. A number of 3D structures are now available of ternary complexes between TCRs and peptide:major histocompatibility complexes (pMHC). Here, to glean molecular-level insights we analyze structures of TCRs bound to human class I nonamer peptide-MHC complexes. Residues at peptide positions 4 to 8 are found to be particularly important for TCR binding. About 90% of the TCRs hydrogen bond with one or both of the peptide residues at positions 4 and 8 presented by MHC allele HLA-A2, and this number is still ~79% for peptides presented by other MHC alleles. Residue 8, which lies outside the previously-identified central peptide region, is crucial for TCR recognition of class I MHC-presented nonamer peptides. The statistics of the interactions also sheds light on the MHC residues important for TCR binding. The present analysis will aid in the structural modeling of TCR:pMHC complexes and has implications for the rational design of peptide-based vaccines and T cell-based immunotherapies.
PMID:35403257 | DOI:10.1002/prot.26343
