Portal de Periódicos da CAPES

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

2016; American Association for the Advancement of Science; Volume: 351; Issue: 6274 Linguagem: Inglês

10.1126/science.aac9475

1095-9203

Scott G. Hansen, Helen L. Wu, Benjamin J. 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 K. Axthelm, Jay A. Nelson, Geraldine M. Gillespie, Lucy C. Walters, Simon Brackenridge, Hannah Sharpe, César A. López, Klaus Früh, Bette Korber, Andrew J. McMichael, S. Gnanakaran, Jonah B. Sacha, Louis J. Picker,

Immunotherapy and Immune Responses

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.