T-cell receptor specific for HIV-1 Tat-derived peptides (Tat-specific TCR)

T-cell receptors (TCRs) specific for HIV-1 Tat-derived peptides are engineered or naturally occurring receptors designed to recognize the Trans-activator of transcription (Tat) protein of HIV-1. Tat is an essential regulatory protein expressed early in the viral life cycle, making it an ideal target for eliminating infected cells before significant viral production and MHC downregulation by Nef occur (Addo et al., 2001). These TCRs typically recognize specific Tat epitopes, such as the HLA-A*02:01-restricted peptide Tat (38-47) (ITKGLGISYG), presented on the surface of infected CD4+ T cells. In therapeutic applications, such as TCR-T cell therapy or soluble bispecifics like ImmTAV (Immune mobilising monoclonal TCRs Against Virus), these receptors redirect the immune system to identify and kill HIV-infected cells, including those in the latent reservoir (Immunocore, 2022). Clinical and preclinical studies have shown that Tat-specific T-cell responses correlate with better viral control and delayed disease progression (Allen et al., 2000). However, challenges include the potential for viral escape through epitope mutations and the risk of off-target toxicity if the TCR cross-reacts with human self-peptides.

Other names

HIV-1 Tat TCRTat-targeted TCRTat-specific T-cell receptorHIV-1 Tat-specific TCR

Recognition of HIV-1 Tat peptides (e.g., Tat 38-47) presented by MHC class I molecules (e.g., HLA-A*02:01) on the surface of infected cells, leading to T-cell activation, secretion of cytokines (IFN-gamma, IL-2), and granzyme/perforin-mediated lysis of the target cell.