HIV-1 Gag-specific T cell receptor (HIV-1 Gag TCR) (HIV-1 Gag TCR)

T cell receptors (TCRs) recognizing HIV-1 Gag-derived peptides presented by Major Histocompatibility Complex (MHC) molecules are essential for the immune system's ability to detect and destroy HIV-infected cells (Walker & McMichael, 2012). These receptors specifically bind to viral epitopes, such as the immunodominant SL9 peptide, when they are displayed on the cell surface by specific HLA alleles like HLA-A*02:01 (Varela-Rohena et al., 2008). In therapeutic contexts, these TCRs are being harnessed through TCR-engineered T cell therapies and bispecific molecules like ImmTAVs (e.g., IMC-HIV) to provide a more potent and directed immune response than what is naturally occurring (Yang et al., 2022). By targeting the Gag protein, which is relatively conserved and highly expressed during the viral life cycle, these therapies aim to reduce the latent HIV reservoir and potentially lead to a functional cure. However, the effectiveness of these treatments can be hindered by the rapid mutation of HIV, leading to epitope escape, and the risk of off-target toxicity if the TCR cross-reacts with similar human peptides (Immunocore, 2023). Furthermore, the requirement for specific HLA matching limits the patient population that can benefit from a particular TCR-based intervention.

Other names

Gag-specific TCRSL9-specific TCRHIV-1 Gag-peptide-MHC complex-specific T-cell receptorT cell receptors recognizing HIV-1 Gag-derived peptides presented by MHC

Engineered TCRs or bispecific molecules redirect T-cell cytotoxicity to recognize and eliminate HIV-infected cells by binding to Gag-derived peptides presented on MHC Class I molecules.