Broadly targeted CD8+ T cell responses restricted by major histocompatibility complex E

Scott Hansen, Helen L. Wu, Benjamin Burwitz, Colette M. Hughes, Katherine B. Hammond, Abigail B. Ventura, Jason S. Reed, Roxanne M. Gilbride, Emily Ainslie, David W. Morrow, Julia C. Ford, Andrea N. Selseth, Reesab Pathak, Daniel Malouli, Alfred W. Legasse, Michael Axthelm, Jay Nelson, Geraldine M. Gillespie, Lucy C. Walters, Simon BrackenridgeHannah R. Sharpe, César A. López, Klaus Frueh, Bette T. Korber, Andrew J. McMichael, S. Gnanakaran, Jonah Sacha, Louis Picker

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Major histocompatibility complex E (MHC-E) is a highly conserved, ubiquitously expressed, nonclassical MHC class Ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (NK) cells. We found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes Rh157.5 and Rh157.4 are deleted results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8αβ+ T cells, at ∼4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side-chain interactions within a stable, open binding groove. Because MHC-E is up-regulated to evade NK cell activity in cells infected with HIV, simian immunodeficiency virus, and other persistent viruses, MHC-E-restricted CD8+ T cell responses have the potential to exploit pathogen immune-evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.

Original languageEnglish (US)
Pages (from-to)714-720
Number of pages7
JournalScience
Volume351
Issue number6274
DOIs
Publication statusPublished - Feb 12 2016

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