CD8+ alpha-beta T-cell receptor specific for HIV epitopes (HIV-specific TCR)

CD8+ alpha-beta T-cell receptors (TCRs) specific for HIV epitopes are specialized heterodimeric proteins expressed on the surface of cytotoxic T lymphocytes (CTLs) that recognize HIV-derived peptides presented by Major Histocompatibility Complex (MHC) class I molecules. These receptors play a critical role in the natural immune response to HIV-1 by identifying infected cells for destruction, particularly those presenting conserved epitopes from viral proteins like Gag, Pol, and Env (Varela-Rohena et al., Nature Medicine, 2008). In therapeutic development, these TCRs are isolated, modified for higher affinity, and used to engineer patient T cells (TCR-T therapy) or incorporated into bispecific molecules like Immune Mobilizing Monoclonal TCRs Against Virus (ImmTAVs) to enhance the clearance of HIV-infected cells (Health et al., Journal of Clinical Investigation, 2019). Such strategies aim to address the limitations of the endogenous immune system, such as T-cell exhaustion and viral mutational escape, which allow the virus to persist in latent reservoirs. Clinical applications, such as the STRIVE trial for IMC-M113V, focus on achieving a functional cure or long-term viral suppression by redirecting the immune system to target stable viral epitopes across different HLA backgrounds, most commonly HLA-A*02 (Immunocore, 2025).

Other names

HIV-specific T-cell receptorHIV-1 specific TCRCD8+ TCR specific for HIV-1 antigensGag-specific TCRSL9-specific TCR

Engineered T-cells or bispecific molecules utilize high-affinity TCRs to recognize HIV-derived peptides (e.g., Gag SL9) presented by MHC class I molecules (e.g., HLA-A*02:01) on infected cells, leading to targeted lysis of the viral reservoir (Immunocore, 2025; Varela-Rohena et al., Nature Medicine, 2008).