Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30479346.
- Also identified by DOI 10.1038/s41467-018-07209-7 and PMC identifier 6258674.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> T cell responses against the immunodominant HIV-1 Gag epitope TL9 (TPQDLNTML<sub>180-188</sub>) 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.
Medical subject headings
- HIV-1
- HLA-B Antigens
- Mutation
- Receptors, Antigen, T-Cell
- gag Gene Products, Human Immunodeficiency Virus