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1ymm
From Proteopedia
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TCR/HLA-DR2b/MBP-peptide complex
Contents |
Overview
Autoimmune diseases are caused by self-reactive lymphocytes that have, escaped deletion. Here we have determined the structure of the, trimolecular complex for a T cell receptor (TCR) from a patient with, multiple sclerosis that causes autoimmunity in transgenic mice. The, structure showed a TCR topology notably different from that of, antimicrobial TCRs. Rather than being centered on the peptide-major, histocompatibility complex, this TCR contacted only the N-terminal peptide, segment and made asymmetrical interactions with the major, histocompatibility complex helices. The interaction was dominated by the, hypervariable complementarity-determining region 3 loops, indicating that, unconventional topologies are possible because of the unique, complementarity-determining region 3 sequences created during, rearrangement. This topology reduces the interaction surface with peptide, and alters the geometry for CD4 association. We propose that unusual, TCR-binding properties can permit autoreactive T cells to escape deletion.
Disease
Known diseases associated with this structure: Chronic infections, due to MBL deficiency OMIM:[154545], Diabetes mellitus, gestational, susceptibility to OMIM:[154545], Mannose-binding protein deficiency OMIM:[154545], Meningococcal disease, susceptibility to OMIM:[154545]
About this Structure
1YMM is a Protein complex structure of sequences from Homo sapiens with NAG as ligand. Full crystallographic information is available from OCA.
Reference
Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor., Hahn M, Nicholson MJ, Pyrdol J, Wucherpfennig KW, Nat Immunol. 2005 May;6(5):490-6. Epub 2005 Apr 10. PMID:15821740
Page seeded by OCA on Mon Nov 12 20:21:49 2007
