T-cell receptor recognizing HIV-1 Gag-derived peptide–MHC complex (HIV-1 Gag TCR)

T-cell receptors (TCRs) recognizing HIV-1 Gag-derived peptide–MHC complexes are specialized immune receptors that identify HIV-infected cells by binding to viral Gag peptides presented on Major Histocompatibility Complex (MHC) molecules. Gag is a primary structural protein of HIV-1, and its relative conservation makes it an ideal target for immunotherapy, particularly the immunodominant SL9 epitope (SLYNTVATL) presented by HLA-A*02:01 (PNAS, 2022; Nature Medicine, 2008). These TCRs are utilized in advanced therapeutic strategies such as TCR-engineered T-cell (TCR-T) therapy and soluble bispecific TCR molecules, such as Immunocore's ImmTAV platform (e.g., IMC-M113V) (Immunocore, 2023; NIH, 2026). In these applications, the TCR is often engineered for enhanced affinity to ensure robust recognition of the low-density pMHC complexes found on latently infected cells (Science Reports, 2022). The primary goal of targeting these complexes is to eliminate the latent HIV reservoir, which remains the main obstacle to a functional cure (CROI, 2025). Clinical evaluation of these therapies has shown promising safety profiles and evidence of T-cell engagement, although challenges such as viral escape through epitope mutation and the risk of cytokine release syndrome remain significant hurdles (Frontiers in Immunology, 2021; NIH, 2014).

Other names

HIV-1 Gag-specific T-cell receptorSL9-specific TCRGag-specific TCRHIV-1 Gag pMHC-specific TCRAnti-HIV-1 Gag TCR

Redirection of T-cell-mediated cytotoxicity toward HIV-infected cells through the specific recognition of Gag-derived peptides (e.g., SL9) presented by MHC class I molecules (e.g., HLA-A*02:01).