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3o6f

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3o6f, resolution 2.80Å ()
Gene: HLA-DRA, HLA-DRA1 (Homo sapiens), HLA-DRB1 (Homo sapiens), TRAC, TCRA (Homo sapiens), TRBC1 (Homo sapiens)


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

Crystal structure of a human autoimmune TCR MS2-3C8 bound to MHC class II self-ligand MBP/HLA-DR4

Publication Abstract from PubMed

The failure to eliminate self-reactive T cells during negative selection is a prerequisite for autoimmunity. To escape deletion, autoreactive T-cell receptors (TCRs) may form unstable complexes with self-peptide-MHC by adopting suboptimal binding topologies compared with anti-microbial TCRs. Alternatively, escape can occur by weak binding between self-peptides and MHC. We determined the structure of a human autoimmune TCR (MS2-3C8) bound to a self-peptide from myelin basic protein (MBP) and the multiple sclerosis-associated MHC molecule HLA-DR4. MBP is loosely accommodated in the HLA-DR4-binding groove, accounting for its low affinity. Conversely, MS2-3C8 binds MBP-DR4 as tightly as the most avid anti-microbial TCRs. MS2-3C8 engages self-antigen via a docking mode that resembles the optimal topology of anti-foreign TCRs, but is distinct from that of other autoreactive TCRs. Combined with a unique CDR3beta conformation, this docking mode compensates for the weak binding of MBP to HLA-DR4 by maximizing interactions between MS2-3C8 and MBP. Thus, the MS2-3C8-MBP-DR4 complex reveals the basis for an alternative strategy whereby autoreactive T cells escape negative selection, yet retain the ability to initiate autoimmunity.

Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection., Yin Y, Li Y, Kerzic MC, Martin R, Mariuzza RA, EMBO J. 2011 Feb 4. PMID:21297580

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3o6f is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Yin Y, Li Y, Kerzic MC, Martin R, Mariuzza RA. Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection. EMBO J. 2011 Feb 4. PMID:21297580 doi:10.1038/emboj.2011.21

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