5C0G: Hla-a02 Carrying Ylggpdfpti

Citation:
Abstract
The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide-major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I-restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key-like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease.
PDB ID: 5C0GDownload
MMDB ID: 138813
PDB Deposition Date: 2015/6/12
Updated in MMDB: 2016/06
Experimental Method:
x-ray diffraction
Resolution: 1.37  Å
Source Organism:
Similar Structures:
Biological Unit for 5C0G: trimeric; determined by software (PISA)
Molecular Components in 5C0G
Label Count Molecule
Proteins (3 molecules)
1
HLA Class I Histocompatibility Antigen, A-2 Alpha Chain(Gene symbol: HLA-A)
Molecule annotation
1
Beta-2-microglobulin(Gene symbol: B2M)
Molecule annotation
1
Marker Peptide
Molecule annotation
Chemicals (15 molecules)
1
14
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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