Work

Kinetically distinct processing pathways diversify the CD8 + T cell response to a single viral epitope

Year: 2020

Type: article

Abstract: Significance CD8 + T cells eliminate infections and cancers through recognition of antigen-derived peptides displayed at the cell surface in combination with MHC class I molecules. We show that a single glycoprotein-derived epitope is generated from two sources: 1) the conventional cohort that is delivered to the endoplasmic reticulum, a fraction failing quality control and undergoing ERAD, and 2) an exceedingly minor fraction that is mislocalized to the cytosol during translation and immediately degraded. Notably, peptide derived from mislocalized antigen is delivered to the cell surface with faster kinetics and drives greater CD8 + T cell expansion and functionality. These findings provide key insights for development of vaccines intended to elicit CD8 + T cell-mediated protection.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2004372117

Authors: Gabriela L. Cosma, Jenna L. Lobby, Elizabeth J. Fay, Nicholas A. Siciliano, Ryan A. Langlois, Laurence C. Eisenlohr

Institutions: Children's Hospital of Philadelphia, Thomas Jefferson University, University of Minnesota, University of Pennsylvania

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Allergy and Infectious Diseases