Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor.
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Hahn M, Nicholson MJ, Pyrdol J, Wucherpfennig KW
Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor.
Nat Immunol. 2005 May;6(5):490-6. doi: 10.1038/ni1187. Epub 2005 Apr 10.
- PubMed ID
- 15821740 [ View in PubMed]
- Abstract
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.