Dual HLA B(star)42 and B(star)81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants
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| Authors: | Ogunshola, F; Anmole, G; Miller, RL; Goering, E; Nkosi, T; Muema, D; Mann, J; Ismail, N; Chopera, D; Ndung'u, T; Brockman, MA; Ndhlovu, ZM |
| Year: | 2018 |
| Journal: | Nat. Commun. 9 Article Link (DOI) PubMed |
| Title: | Dual HLA B(star)42 and B(star)81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants |
| Abstract: | Some closely related human leukocyte antigen (HLA) alleles are associated with variable clinical outcomes following HIV-1 infection despite presenting the same viral epitopes. Mechanisms underlying these differences remain unclear but may be due to intrinsic characteristics of the HLA alleles or responding T cell repertoires. Here we examine CD8(+) T cell responses against the immunodominant HIV-1 Gag epitope TL9 (TPQDLNTML(180-188)) in the context of the protective allele B(star)81:01 and the less protective allele B(star)42:01. We observe a population of dual-reactive T cells that recognize TL9 presented by both B(star)81:01 and B(star)42:01 in individuals lacking one allele. The presence of dual-reactive T cells is associated with lower plasma viremia, suggesting a clinical benefit. In B(star)42:01 expressing individuals, the dual-reactive phenotype defines public T cell receptor (TCR) clones that recognize a wider range of TL9 escape variants, consistent with enhanced control of viral infection through containment of HIV-1 sequence adaptation. |
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