Redox Regulation Facilitates Optimal Peptide Selection by MHC Class I during Antigen Processing

Boyoun Park, Sungwook Lee, Eunkyung Kim, Kwangmin Cho, Stanley R. Riddell, Sunglim Cho, Kwangseog Ahn

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)


Activated CD8+ T cells discriminate infected and tumor cells from normal self by recognizing MHC class I-bound peptides on the surface of antigen-presenting cells. The mechanism by which MHC class I molecules select optimal peptides against a background of prevailing suboptimal peptides and in a considerably proteolytic ER environment remained unknown. Here, we identify protein disulfide isomerase (PDI), an enzyme critical to the formation of correct disulfide bonds in proteins, as a component of the peptide-loading complex. We show that PDI stabilizes a peptide-receptive site by regulating the oxidation state of the disulfide bond in the MHC peptide-binding groove, a function that is essential for selecting optimal peptides. Furthermore, we demonstrate that human cytomegalovirus US3 protein inhibits CD8+ T cell recognition by mediating PDI degradation, verifying the functional relevance of PDI-catalyzed peptide editing in controlling intracellular pathogens. These results establish a link between thiol-based redox regulation and antigen processing.

Original languageEnglish
Pages (from-to)369-382
Number of pages14
Issue number2
Publication statusPublished - 2006 Oct 20

Bibliographical note

Funding Information:
We thank Y. Nomura for PDI cDNA constructs, M. Theobald for MZ1851 RC cell lines, and P. Cresswell for anti-tapasin antibodies. We also thank Drs. L. Ruddock, T. Dick, and P. Cresswell for helpful discussions. This work was supported by National Creative Research Initiative Program of MOST/KOSEF. E.K. was supported by the BK21 fellowship.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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