2OL3

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

Summary for 2OL3

• Entry DOI: 10.2210/pdb2ol3/pdb
• Descriptor: BM3.3 T-CELL RECEPTOR ALPHA-CHAIN, BM3.3 T-CELL RECEPTOR BETA-CHAIN, ALLOGENEIC H-2KBM8 MHC CLASS I MOLECULE, ... (7 entities in total)
• Functional Keywords: t cell receptor, class i mhc, h-2kbm8, tcr-pmhc complex, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 5
• Total formula weight: 73808.11

Authors

Mazza, C.,Auphan-Anezin, N.,Gregoire, C.,Guimezanes, A.,Kellenberger, C.,Roussel, A.,Kearney, A.,Van der Merwe, P.A.,Schmitt-Verhulst, A.M.,Malissen, B. (deposition date: 2007-01-18, release date: 2007-04-03, Last modification date: 2024-10-30)

Primary citation

Mazza, C.,Auphan-Anezin, N.,Gregoire, C.,Guimezanes, A.,Kellenberger, C.,Roussel, A.,Kearney, A.,van der Merwe, P.A.,Schmitt-Verhulst, A.M.,Malissen, B.
How much can a T-cell antigen receptor adapt to structurally distinct antigenic peptides?
Embo J., 26:1972-1983, 2007

PubMed Abstract: 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.

PubMed: 17363906
DOI: 10.1038/sj.emboj.7601605

Experimental method

X-RAY DIFFRACTION (2.9 Å)