1ZGL

Crystal structure of 3A6 TCR bound to MBP/HLA-DR2a

Summary for 1ZGL

• Entry DOI: 10.2210/pdb1zgl/pdb
• Related: 1FYT 1U3H
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, major histocompatibility complex, class II, DR beta 5, Myelin basic protein, ... (5 entities in total)
• Functional Keywords: tcr-peptide-mhc complex, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 20
• Total formula weight: 383726.25

Authors

Li, Y.,Huang, Y.,Lue, J.,Quandt, J.A.,Martin, R.,Mariuzza, R.A. (deposition date: 2005-04-21, release date: 2005-10-18, Last modification date: 2024-11-13)

Primary citation

Li, Y.,Huang, Y.,Lue, J.,Quandt, J.A.,Martin, R.,Mariuzza, R.A.
Structure of a human autoimmune TCR bound to a myelin basic protein self-peptide and a multiple sclerosis-associated MHC class II molecule.
Embo J., 24:2968-2979, 2005

PubMed Abstract: Multiple sclerosis is mediated by T-cell responses to central nervous system antigens such as myelin basic protein (MBP). To investigate self-peptide/major histocompatibility complex (MHC) recognition and T-cell receptor (TCR) degeneracy, we determined the crystal structure, at 2.8 A resolution, of an autoimmune TCR (3A6) bound to an MBP self-peptide and the multiple sclerosis-associated MHC class II molecule, human leukocyte antigen (HLA)-DR2a. The complex reveals that 3A6 primarily recognizes the N-terminal portion of MBP, in contrast with antimicrobial and alloreactive TCRs, which focus on the peptide center. Moreover, this binding mode, which may be frequent among autoimmune TCRs, is compatible with a wide range of orientation angles of TCR to peptide/MHC. The interface is characterized by a scarcity of hydrogen bonds between TCR and peptide, and TCR-induced conformational changes in MBP/HLA-DR2a, which likely explain the low observed affinity. Degeneracy of 3A6, manifested by recognition of superagonist peptides bearing substitutions at nearly all TCR-contacting positions, results from the few specific interactions between 3A6 and MBP, allowing optimization of interface complementarity through variations in the peptide.

PubMed: 16079912
DOI: 10.1038/sj.emboj.7600771

Experimental method

X-RAY DIFFRACTION (2.8 Å)