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

The T-cell receptor (TCR) recognizing HIV peptide–MHC complexes is a specialized antigen-recognition molecule found on the surface of CD8+ T cells that plays a critical role in the adaptive immune response to HIV-1. It functions by specifically binding to viral peptides, such as the Gag-derived SL9 epitope, when they are presented by Major Histocompatibility Complex (MHC) class I molecules (typically HLA-A*02:01) on the surface of infected cells (Varela-Rohena et al., 2008). This recognition event triggers a signaling cascade that leads to T-cell activation, proliferation, and the release of cytotoxic granules to eliminate the infected host cell. In chronic HIV infection, the effectiveness of these TCRs is often compromised by viral escape mutations and the induction of T-cell exhaustion, which contributes to the persistence of the viral reservoir. Therapeutic strategies targeting this receptor include synthetic T-cell activators (synTacs) and Immuno-STATs, which are designed to selectively expand and activate functional HIV-specific T cells (SynTac, 2021). Additionally, engineered versions of these TCRs are utilized in adoptive cell therapies (TCR-T) and soluble bispecific molecules (ImmTAVs) to redirect the immune system toward the viral reservoir, representing a promising avenue for achieving a functional cure for HIV (Immunocore, 2022). Safety concerns associated with these therapies include off-target toxicity due to cross-reactivity with self-peptides and the risk of cytokine release syndrome.

Other names

HIV-TCRHIV-specific T-cell receptorGag-specific T-cell receptorSL9-specific T-cell receptorHIV peptide-MHC-specific T-cell receptor

T-cell activation, expansion, and redirection to HIV-infected cells