1. Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants.
- Author
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Ogunshola F, Anmole G, Miller RL, Goering E, Nkosi T, Muema D, Mann J, Ismail N, Chopera D, Ndung'u T, Brockman MA, and Ndhlovu ZM
- Subjects
- Adult, Amino Acid Sequence, CD8-Positive T-Lymphocytes immunology, Clone Cells, Female, Humans, Male, Reproducibility of Results, Viral Load, Young Adult, gag Gene Products, Human Immunodeficiency Virus chemistry, HIV-1 metabolism, HLA-B Antigens immunology, Mutation genetics, Receptors, Antigen, T-Cell metabolism, gag Gene Products, Human Immunodeficiency Virus genetics
- 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 (TPQDLNTML180-188 ) in the context of the protective allele B*81:01 and the less protective allele B*42:01. We observe a population of dual-reactive T cells that recognize TL9 presented by both B*81:01 and B*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*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.- Published
- 2018
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