MHC restriction is structurally encoded by the T cell receptor germline
MHC restriction -- the requirement for {beta} T cell receptors (TCRs) to recognize Major Histocompatibility Complex (MHC) molecules when presenting peptide antigens -- is a pillar of adaptive immunity. Here, we provide direct structural evidence for TCR germline-encoded recognition of MHC molecules irrespective of antigenic peptide. We engineered "germline-like" TCRs to eliminate CDR3 specificity…
Major Histocompatibility Complex (MHC) restriction, a critical aspect of adaptive immunity, is determined by the T cell receptor (TCR) germline. Researchers have now provided direct structural evidence demonstrating that TCRs, without relying on the peptide antigen, can recognize MHC molecules. By engineering germline-like TCRs to remove specificity for the peptide and employing a molecular clamping technique to trap ultra-low-affinity complexes for cryo-EM, the team discovered that TCR/pMHC docking modes remain identical to those of wild-type TCRs, regardless of the antigenic peptide and MHC allele.
This finding suggests that the TCR germline carries the blueprint for MHC restriction, offering a sequence-based framework that could potentially aid in computational and AI-driven prediction of TCR specificity.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
