3ws3

From Proteopedia

Jump to: navigation, search

Crystal Structure of H-2D in complex with an insulin derived peptide

Structural highlights

3ws3 is a 6 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.335Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HA11_MOUSE Involved in the presentation of foreign antigens to the immune system.

Publication Abstract from PubMed

Self-reactive T cells must escape thymic negative selection to mediate pathogenic autoimmunity. In the NOD mouse model of autoimmune diabetes, several beta cell-cytotoxic CD8 T cell populations are known, with the most aggressive of these represented by AI4, a T cell clone with promiscuous Ag-recognition characteristics. We identified a long-elusive beta cell-specific ligand for AI4 as an unusually short H-2D(b)-binding 7-mer peptide lacking a C-terminal anchor residue and derived from the insulin A chain (InsA14-20). Crystallography reveals that compensatory mechanisms permit peptides lacking a C-terminal anchor to bind sufficiently to the MHC to enable destructive T cell responses, yet allow cognate T cells to avoid negative selection. InsA14-20 shares two solvent-exposed residues with previously identified AI4 ligands, providing a structural explanation for AI4's promiscuity. Detection of AI4-like T cells, using mimotopes of InsA14-20 with improved H-2D(b)-binding characteristics, establishes the AI4-like T cell population as a consistent feature of the islet infiltrates of NOD mice. Our work establishes undersized peptides as previously unrecognized targets of autoreactive CD8 T cells and presents a strategy for their further exploration as Ags in autoimmune disease.

Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to mediate pathogenic autoreactive T cell responses.,Lamont D, Mukherjee G, Kumar PR, Samanta D, McPhee CG, Kay TW, Almo SC, DiLorenzo TP, Serreze DV J Immunol. 2014 Sep 1;193(5):2135-46. doi: 10.4049/jimmunol.1400997. Epub 2014, Jul 25. PMID:25063871[1]

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

Loading citation details..
Citations
reviews cite this structure
No citations found

See Also

References

  1. Lamont D, Mukherjee G, Kumar PR, Samanta D, McPhee CG, Kay TW, Almo SC, DiLorenzo TP, Serreze DV. Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to mediate pathogenic autoreactive T cell responses. J Immunol. 2014 Sep 1;193(5):2135-46. doi: 10.4049/jimmunol.1400997. Epub 2014, Jul 25. PMID:25063871 doi:http://dx.doi.org/10.4049/jimmunol.1400997

Contents


PDB ID 3ws3

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools