crystal structure of BM3.3 ScFV TCR in complex with PBM8-H-2KBM8 MHC class I molecule

File:2ol3.gif


2ol3, resolution 2.90Å

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OverviewOverview

Binding 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.

About this StructureAbout this Structure

2OL3 is a Protein complex structure of sequences from Mus musculus with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

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 Mar 15;. PMID:17363906

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