4PG2

The crystal structure of H-2Db with a S-glutathionylated peptide

Summary for 4PG2

• Entry DOI: 10.2210/pdb4pg2/pdb
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, CYS-SER-LEU-TRP-ASN-GLY-PRO-HIS-LEU, ... (6 entities in total)
• Functional Keywords: immune receptor, glutathionylated peptide, t cell biology, antigen presentation, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 3
• Total formula weight: 45500.89

Authors

Theodossis, A.,Rossjohn, J. (deposition date: 2014-05-01, release date: 2014-09-10, Last modification date: 2023-12-27)

Primary citation

Trujillo, J.A.,Croft, N.P.,Dudek, N.L.,Channappanavar, R.,Theodossis, A.,Webb, A.I.,Dunstone, M.A.,Illing, P.T.,Butler, N.S.,Fett, C.,Tscharke, D.C.,Rossjohn, J.,Perlman, S.,Purcell, A.W.
The cellular redox environment alters antigen presentation.
J.Biol.Chem., 289:27979-27991, 2014

PubMed Abstract: Cysteine-containing peptides represent an important class of T cell epitopes, yet their prevalence remains underestimated. We have established and interrogated a database of around 70,000 naturally processed MHC-bound peptides and demonstrate that cysteine-containing peptides are presented on the surface of cells in an MHC allomorph-dependent manner and comprise on average 5-10% of the immunopeptidome. A significant proportion of these peptides are oxidatively modified, most commonly through covalent linkage with the antioxidant glutathione. Unlike some of the previously reported cysteine-based modifications, this represents a true physiological alteration of cysteine residues. Furthermore, our results suggest that alterations in the cellular redox state induced by viral infection are communicated to the immune system through the presentation of S-glutathionylated viral peptides, resulting in altered T cell recognition. Our data provide a structural basis for how the glutathione modification alters recognition by virus-specific T cells. Collectively, these results suggest that oxidative stress represents a mechanism for modulating the virus-specific T cell response.

PubMed: 25135637
DOI: 10.1074/jbc.M114.573402

Experimental method

X-RAY DIFFRACTION (2.8 Å)