T cell receptors for the HIV KK10 epitope from patients with differential immunologic control are functionally indistinguishable
Year: 2018
Type: article
Abstract: HIV controllers (HCs) are individuals who can naturally control HIV infection, partially due to potent HIV-specific CD8+ T cell responses. Here, we examined the hypothesis that superior function of CD8+ T cells from HCs is encoded by their T cell receptors (TCRs). We compared the functional properties of immunodominant HIV-specific TCRs obtained from HLA-B*2705 HCs and chronic progressors (CPs) following expression in primary T cells. T cells transduced with TCRs from HCs and CPs showed equivalent induction of epitope-specific cytotoxicity, cytokine secretion, and antigen-binding properties. Transduced T cells comparably, albeit modestly, also suppressed HIV infection in vitro and in humanized mice. We also performed extensive molecular dynamics simulations that provided a structural basis for similarities in cytotoxicity and epitope cross-reactivity. These results demonstrate that the differential abilities of HIV-specific CD8+ T cells from HCs and CPs are not genetically encoded in the TCRs alone and must depend on additional factors.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: California Institute of Technology, Harvard University, Harvard University Center for AIDS Research, California Institute of Regenerative Medicine, Leidos, National Institutes of Health, Center for AIDS Research, University of Washington, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, Center for AIDS Research, University of California Los Angeles
OpenAlex ID: W2787064560