Coreceptor affinity for MHC defines peptide specificity requirements for TCR interaction with coagonist peptide–MHC

• DOI: 10.1084/jem.20122528
• Publication Date: 2013-08-13T03:19:13Z
• Authors: John A.H. Hoerter; Joanna Brzostek; Maxim N. Artyomov; Steven M. Abel; Javier Casas; Vasily Rybakin; Jeanette Ampudia; Carina Lotz; Janet M. Connolly; Arup K. Chakraborty; Keith G. Gould; Nicholas R.J. Gas...
• Keywords: MHC restriction

Recent work has demonstrated that nonstimulatory endogenous peptides can enhance T cell recognition of antigen, but MHCI- and MHCII-restricted systems have generated very different results. TCRs need to interact with the peptide–MHC (pMHC), showing peptide specificity for activation enhancers or coagonists. In contrast, MHCI-restricted cells studied date show no such coagonists, suggesting CD8 binding noncognate MHCI is more important. Here we how this dichotomy be resolved by varying TCR agonist coagonists coupled computer simulations, identify two distinct mechanisms which influences coagonism. Mechanism 1 identifies requirement ligand suggests a direct relationship between magnitude coagonism affinity coagonist pMHCI. 2 describes pMHCI changes specific peptides. MHCs bind strongly were tolerant all most as weaker CD8-binding required stronger coagonist, limiting potential These findings in also explain peptide-specific cells, CD4–MHCII interaction generally than CD8–MHCI.