T cell receptors for the HIV KK10 epitope from patients with differential immunologic control are functionally indistinguishable

AV Joglekar, Z Liu, JK Weber… - Proceedings of the …, 2018 - National Acad Sciences
AV Joglekar, Z Liu, JK Weber, Y Ouyang, JD Jeppson, WJ Noh, PA Lamothe-Molina, H Chen…
Proceedings of the National Academy of Sciences, 2018National Acad Sciences
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 …
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.
National Acad Sciences