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crystal structure of BM3.3 ScFV TCR in complex with PBM8-H-2KBM8 MHC class I moleculecrystal structure of BM3.3 ScFV TCR in complex with PBM8-H-2KBM8 MHC class I molecule
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBinding degeneracy is thought to constitute a fundamental property of the T-cell antigen receptor (TCR), yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and a peptide (pBM8) bound to the H-2K(bm8) major histocompatibility complex (MHC) molecule, and compared it with the structures of the BM3.3 TCR bound to H-2K(b) molecules loaded with two peptides that had a minimal level of primary sequence identity with pBM8. Our findings provide a refined structural view of the basis of BM3.3 TCR cross-reactivity and a structural explanation for the long-standing paradox that a TCR antigen-binding site can be both specific and degenerate. We also measured the thermodynamic features and biological penalties that incurred during cross-recognition. Our data illustrate the difficulty for a given TCR in adapting to distinct peptide-MHC surfaces while still maintaining affinities that result in functional in vivo responses. Therefore, when induction of protective effector T cells is used as the ultimate criteria for adaptive immunity, TCRs are probably much less degenerate than initially assumed. How much can a T-cell antigen receptor adapt to structurally distinct antigenic peptides?,Mazza C, Auphan-Anezin N, Gregoire C, Guimezanes A, Kellenberger C, Roussel A, Kearney A, van der Merwe PA, Schmitt-Verhulst AM, Malissen B EMBO J. 2007 Apr 4;26(7):1972-83. Epub 2007 Mar 15. PMID:17363906[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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