4GRL
Crystal structure of a autoimmune TCR-MHC complex
Summary for 4GRL
| Entry DOI | 10.2210/pdb4grl/pdb |
| Related | 3PL6 4MAY |
| Descriptor | MHC class II HLA-DQ-alpha chain, MHC class II antigen, TCR Hy.1B11 alpha chain, ... (6 entities in total) |
| Functional Keywords | immune complex, peptide antigen presentation, multiple sclerosis, autoimmunity, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 97019.84 |
| Authors | Sethi, D.K.,Wucherpfennig, K.W. (deposition date: 2012-08-25, release date: 2013-11-06, Last modification date: 2024-10-30) |
| Primary citation | Sethi, D.K.,Gordo, S.,Schubert, D.A.,Wucherpfennig, K.W. Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop. Nat Commun, 4:2623-2623, 2013 Cited by PubMed Abstract: 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 (CDR3α 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 (CDR3α 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. PubMed: 24136005DOI: 10.1038/ncomms3623 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.86 Å) |
Structure validation
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