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Publication Abstract from PubMed

Successful immunity requires that a limited pool of alphabeta T-cell receptors (TCRs) provide cover for a vast number of potential foreign peptide antigens presented by 'self' major histocompatibility complex (pMHC) molecules. Structures of unligated and ligated MHC class-I-restricted TCRs with different ligands, supplemented with biophysical analyses, have revealed a number of important mechanisms that govern TCR mediated antigen recognition. HA1.7 TCR binding to the influenza hemagglutinin antigen (HA(306-318)) presented by HLA-DR1 or HLA-DR4 represents an ideal system for interrogating pMHC-II antigen recognition. Accordingly, we solved the structure of the unligated HA1.7 TCR and compared it to both complex structures. Despite a relatively rigid binding mode, HA1.7 T-cells could tolerate mutations in key contact residues within the peptide epitope. Thermodynamic analysis revealed that limited plasticity and extreme favorable entropy underpinned the ability of the HA1.7 T-cell clone to cross-react with HA(306-318) presented by multiple MHC-II alleles.

Minimal conformational plasticity enables TCR cross-reactivity to different MHC class II heterodimers.,Holland CJ, Rizkallah PJ, Vollers S, Calvo-Calle JM, Madura F, Fuller A, Sewell AK, Stern LJ, Godkin A, Cole DK Sci Rep. 2012;2:629. doi: 10.1038/srep00629. Epub 2012 Sep 4. PMID:22953050^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.