HIV infects and depletes CD4+ T cells and currently almost 38 million people live with HIV worldwide1. Antiretroviral therapy (ART) has dramatically improved the health of HIV-infected individuals, however, many side-effects are arising from prolonged use showing the urgent need to develop new treatments and ideally, a vaccine for this virus2.
Rare individuals, termed HIV controllers, can control HIV viral load and remain healthy despite the infection in the absence of ART. Despite Human Leukocyte Antigen (HLA) gene diversity in the population, 50% of HIV controllers are expressing the HLA-B57 gene allele3. Gag derived peptide, TW10, is an epitope dominant in early HIV infection, and is presented by HLA-B57. Strong T-cell responses to this epitope result in escape mutations in TW10 that reduce the virus’ fitness4. Given its presentation in early infection, TW10, could therefore shape the long-term control of HIV infection.
As not all HLA-B57+ individuals are HIV controllers, further research into the T cell response towards the TW10 epitope is needed. Here, we study the specific strength and functionality of responses to the TW10 epitope presented by HLA-B57. We determine the T cell receptor (TCR) repertoire of clones specific for HLA-B57-TW10, as well as their polyfunctionality and avidity, and reveal the differences between HIV controllers and non-controllers. Furthermore, by employing surface plasmon resonance and X-ray crystallography we reveal the molecular basis of TW10 recognition by selected TCRs.
The link between HIV control and T cells function, if clearly understood, could be harnessed to manipulate this protective immunity for vaccine design or therapeutics, in order to reproduce a controller-like response.