Structural highlights
4grl is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Related: | 3pl6, 4may |
| Gene: | alpha chain, HLA-DQ1, HLA-DQA1, MHC CLASS II MOLECULE (HUMAN), beta chain, HLA-DQ1, HLA-DQB1, MHC CLASS II MOLECULE (HUMAN), TCR Hy.1B11 alpha chain (HUMAN), TCR Hy.1B11 beta chain (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Publication Abstract from PubMed
Self-reactive CD4 T cells are thought to have a central role in the pathogenesis of many chronic inflammatory human diseases. Microbial peptides can activate self-reactive T cells, but the structural basis for such crossreactivity is not well understood. The Hy.1B11 T cell receptor (TCR) originates from a patient with multiple sclerosis and recognizes the self-antigen myelin basic protein. Here we report the structural mechanism of TCR crossreactivity with two distinct peptides from human pathogens. The structures show that a single TCR residue (CDR3alpha F95) makes the majority of contacts with the self-peptide and both microbial peptides (66.7-80.6%) due to a highly tilted TCR-binding topology on the peptide-MHC surface. Further, a neighbouring residue located on the same TCR loop (CDR3alpha E98) forms an energetically critical interaction with the MHC molecule. These data show how binding by a self-reactive TCR favors crossreactivity between self and microbial antigens.
Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop.,Sethi DK, Gordo S, Schubert DA, Wucherpfennig KW Nat Commun. 2013 Oct 18;4:2623. doi: 10.1038/ncomms3623. PMID:24136005[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sethi DK, Gordo S, Schubert DA, Wucherpfennig KW. Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop. Nat Commun. 2013 Oct 18;4:2623. doi: 10.1038/ncomms3623. PMID:24136005 doi:http://dx.doi.org/10.1038/ncomms3623
