T cell receptor recognizing HIV-1 conserved-region peptides presented by MHC (HIV-TCR)

The T cell receptor (TCR) recognizing HIV-1 conserved-region peptides presented by MHC is a specialized immune receptor that mediates the identification and destruction of HIV-infected cells (Frontiers in Immunology, 2018). These TCRs are characterized by their ability to bind specific viral peptide fragments, such as those derived from the highly conserved Gag or Pol proteins, when they are displayed on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 (PNAS, 2012). In the context of HIV-1 infection, natural TCRs with high affinity for these conserved regions are often found in "elite controllers" who maintain low viral loads without medication (NIH, 2018). Therapeutically, these TCRs are being harnessed through engineered T-cell therapies (TCR-T) and soluble TCR bispecific molecules, such as Immunocore's ImmTAV platform, including the clinical candidate IMC-M113V (Immunocore, 2023). These interventions aim to redirect the immune system to eliminate the latent HIV reservoir, which remains the primary barrier to a functional cure (Molecular Therapy, 2014). The mechanism involves the TCR binding to the peptide-MHC complex, which triggers T-cell activation and the release of cytotoxic molecules like granzymes and perforins to lyse the infected cell (PLOS Pathogens, 2012). However, the effectiveness of these therapies is often limited by the requirement for specific HLA alleles in patients and the potential for "off-target" reactivity against similar self-peptides (Vaccines, 2020). Additionally, the use of latency-reversing agents is often required to induce the expression of viral antigens in hidden reservoirs to ensure effective TCR recognition (NIH, 2019).

Other names

HIV-1 specific T cell receptorGag-specific T cell receptorPol-specific T cell receptorHIV-1 conserved epitope TCRSL9-specific TCRKF11-specific TCR

Recognition of specific HIV-1 peptide-MHC complexes on the surface of infected cells, leading to T-cell activation and granzyme/perforin-mediated lysis of the target cell.