T-cell receptor recognizing HIVACAT T-cell immunogen-derived HIV-1 peptide–MHC complexes (TCR-HTI) (TCR-HTI)

The T-cell receptor (TCR) recognizing HIVACAT T-cell immunogen (HTI)-derived HIV-1 peptide–MHC complexes is a specialized immune receptor that targets highly conserved regions of the HIV-1 virus. The HTI immunogen was designed to include 16 segments of the HIV-1 proteome (Gag, Pol, Vif, and Nef) that are frequently targeted by 'elite controllers'—individuals who naturally suppress viral replication without medication (Mothe et al., 2015, Journal of Translational Medicine). These TCRs, when expressed on CD8+ T-cells, bind to HTI peptides presented by Major Histocompatibility Complex (MHC) class I molecules, leading to the destruction of infected cells. This receptor is the primary target of therapeutic vaccines like AELIX-002, which aims to expand the population of HTI-specific T-cells to achieve a 'functional cure' or long-term viral remission (Bailon et al., 2022, Nature Medicine). Clinical strategies involving this target focus on overcoming HIV's genetic diversity by forcing the immune system to attack regions where mutations would likely result in a significant fitness cost to the virus (ClinicalTrials.gov, NCT03204617). The efficacy of targeting these TCRs is highly dependent on the patient's HLA genotype, as specific MHC alleles are required to present the HTI peptides effectively. Current research is exploring the combination of HTI vaccines with latency-reversing agents or TLR7 agonists like vesatolimod to enhance the clearance of the viral reservoir (AELIX Therapeutics, 2023).

Other names

HTI-specific T-cell receptorHIVACAT T-cell immunogen-specific TCRHIV-1 HTI-specific TCRT-cell receptor recognizing HTI-derived HIV-1 peptide–MHC complexes

Activation of antigen-specific CD8+ T-cells to recognize and eliminate HIV-infected cells via MHC-restricted peptide presentation.