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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 publication

DOI

10.1126/science.aac9475

Type

Journal article

Journal

Science

Publication Date

12/02/2016

Volume

351

Pages

714 - 720

Keywords

Animals, Antigen Presentation, Antigenic Variation, CD8-Positive T-Lymphocytes, Cytomegalovirus, Epitopes, T-Lymphocyte, Genetic Vectors, Histocompatibility Antigens Class I, Host-Pathogen Interactions, Immune Evasion, Killer Cells, Natural, Macaca mulatta, Protein Structure, Secondary, Simian Immunodeficiency Virus, Vaccination