Publication Date:
2016-01-23
Description:
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 CD8alphabeta(+) 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769032/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769032/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Scott G -- Wu, Helen L -- Burwitz, Benjamin J -- Hughes, Colette M -- Hammond, Katherine B -- Ventura, Abigail B -- Reed, Jason S -- Gilbride, Roxanne M -- Ainslie, Emily -- Morrow, David W -- Ford, Julia C -- Selseth, Andrea N -- Pathak, Reesab -- Malouli, Daniel -- Legasse, Alfred W -- Axthelm, Michael K -- Nelson, Jay A -- Gillespie, Geraldine M -- Walters, Lucy C -- Brackenridge, Simon -- Sharpe, Hannah R -- Lopez, Cesar A -- Fruh, Klaus -- Korber, Bette T -- McMichael, Andrew J -- Gnanakaran, S -- Sacha, Jonah B -- Picker, Louis J -- HHSN272201100013C/AI/NIAID NIH HHS/ -- HHSN272201100013C/PHS HHS/ -- P01 AI094417/AI/NIAID NIH HHS/ -- P01-AI094417/AI/NIAID NIH HHS/ -- P50-GM065794/GM/NIGMS NIH HHS/ -- P51 OD011092/OD/NIH HHS/ -- P51-OD011092/OD/NIH HHS/ -- R01 AI059457/AI/NIAID NIH HHS/ -- R01 AI095113/AI/NIAID NIH HHS/ -- R01 AI117802/AI/NIAID NIH HHS/ -- R01 DE021291/DE/NIDCR NIH HHS/ -- R01-AI059457/AI/NIAID NIH HHS/ -- R01-AI095113/AI/NIAID NIH HHS/ -- R01-AI117802/AI/NIAID NIH HHS/ -- R01-DE021291/DE/NIDCR NIH HHS/ -- R37 AI054292/AI/NIAID NIH HHS/ -- R37-AI054292/AI/NIAID NIH HHS/ -- U24 OD010850/OD/NIH HHS/ -- U24-OD010850/OD/NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- UM1-AI100645-01/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):714-20. doi: 10.1126/science.aac9475. Epub 2016 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA. ; Nuffield Department of Medicine, University of Oxford, Oxford OX37FZ, UK. ; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. ; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. The New Mexico Consortium, Los Alamos, NM 87545, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797147" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigen Presentation
;
Antigenic Variation
;
CD8-Positive T-Lymphocytes/*immunology
;
Cytomegalovirus/genetics/*immunology
;
Epitopes, T-Lymphocyte/chemistry/*immunology
;
Genetic Vectors/genetics/immunology
;
Histocompatibility Antigens Class I/chemistry/*immunology
;
Host-Pathogen Interactions/immunology
;
Immune Evasion
;
Killer Cells, Natural/immunology
;
Macaca mulatta
;
Protein Structure, Secondary
;
Simian Immunodeficiency Virus/*immunology
;
Vaccination
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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