The role of MHC-E in T Cell immunity is conserved among humans, rhesus macaques, and cynomolgus macaques
| Autor: | David H. O’Connor, Lina Gao, Alfred W. Legasse, Justin M. Greene, Byung Park, Fidel Ferrer, Roger W. Wiseman, Simon Brackenridge, Katherine B. Hammond, Nicholas J. Maness, Scott G. Hansen, Benjamin N. Bimber, Benjamin J. Burwitz, Michael K. Axthelm, Jason S. Reed, Shaheed A. Abdulhaqq, Andrew J. McMichael, Helen L. Wu, Louis J. Picker, Jonah B. Sacha, Colette M. Hughes, Gabriela M. Webb |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine T cell Immunology Antigen presentation Simian Acquired Immunodeficiency Syndrome chemical and pharmacologic phenomena Human leukocyte antigen CD8-Positive T-Lymphocytes Biology Major histocompatibility complex Article 03 medical and health sciences Antigen Histocompatibility Antigens MHC class I medicine Animals Humans Immunology and Allergy Antigens Viral Cells Cultured Conserved Sequence Antigen Presentation Histocompatibility Antigens Class I Acquired immune system Macaca mulatta Virology Killer Cells Natural Macaca fascicularis 030104 developmental biology medicine.anatomical_structure Models Animal biology.protein Simian Immunodeficiency Virus Peptides CD8 |
| DOI: | 10.4049/jimmunol.1700841 |
| Popis: | MHC-E is a highly conserved nonclassical MHC class Ib molecule that predominantly binds and presents MHC class Ia leader sequence-derived peptides for NK cell regulation. However, MHC-E also binds pathogen-derived peptide Ags for presentation to CD8+ T cells. Given this role in adaptive immunity and its highly monomorphic nature in the human population, HLA-E is an attractive target for novel vaccine and immunotherapeutic modalities. Development of HLA-E–targeted therapies will require a physiologically relevant animal model that recapitulates HLA-E–restricted T cell biology. In this study, we investigated MHC-E immunobiology in two common nonhuman primate species, Indian-origin rhesus macaques (RM) and Mauritian-origin cynomolgus macaques (MCM). Compared to humans and MCM, RM expressed a greater number of MHC-E alleles at both the population and individual level. Despite this difference, human, RM, and MCM MHC-E molecules were expressed at similar levels across immune cell subsets, equivalently upregulated by viral pathogens, and bound and presented identical peptides to CD8+ T cells. Indeed, SIV-specific, Mamu-E–restricted CD8+ T cells from RM recognized antigenic peptides presented by all MHC-E molecules tested, including cross-species recognition of human and MCM SIV-infected CD4+ T cells. Thus, MHC-E is functionally conserved among humans, RM, and MCM, and both RM and MCM represent physiologically relevant animal models of HLA-E–restricted T cell immunobiology. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|