Human Immunodeficiency Virus (HIV) attacks the body’s immune system by targeting the CD4+ T cells. HIV+ patients often must undergo antiretroviral therapy (ART) to reduce and control the viral load to prolong their lifetime along with preventing the viral transmission to others. A rare set of individuals however, known as “HIV controllers” can avoid AIDs disease progression even without ART, and have a low viral load while maintaining high level of CD4+ counts. Investigation of the T cell response in HIV controllers has identified an immunoprevalent HIV epitope known as Gag293presented by multiple HLA-DRs including HLA-DR11, HLA-DR15, HLA-DRB5, HLA-DR1 and HLA-DR7, with a TCR gene expression bias towards the TRAV24 and TRBV2 gene families1.
F24 TCR recognises the Gag293 epitopes presented by different HLA-DR molecules with high affinity2. Our lab has previously carried out extensive structural studies on above complexes using X ray crystallography1. Further studies from our lab have identified highly similar TCR (F13) that only differs by a longer CDR3β loop compared to F24 TCR. This difference led to a different preference for the HLA-DR molecule between the two TCRs. Thus, by using X-ray crystallography, we aim to solve the structure for the complex of F13 TCR-HLA-DR11-RQ13. We have already solved the structure of the F13 TCR alone and have promising data for the complex. The structure will reveal the molecular basis of the HLA interaction and preference that differ from the F24 TCR.
References
Galperin M, Farenc C, Mukhopadhyay M, et al. CD4+ T cell–mediated HLA class II cross-restriction in HIV controllers. Sci Immunol. Published online 2018. doi:10.1126/sciimmunol.aat0687
Benati D, Galperin M, Lambotte O, et al. Public T cell receptors confer high-avidity CD4 responses to HIV controllers. J Clin Invest. 2016;126(6):2093-2108. doi:10.1172/JCI83792