T-cell receptor recognizing HIV-1 Tat peptides in HLA class II (TCR-Tat-MHCII)

The T-cell receptor (TCR) on CD4+ T cells that recognizes HIV-1 Tat-derived peptides presented by HLA class II molecules is a pivotal mediator of the adaptive immune response against Human Immunodeficiency Virus type 1 (HIV-1) [1]. The Tat (Trans-Activator of Transcription) protein is an essential regulatory factor produced early in the viral life cycle, making it a prime target for early detection of infected cells by the immune system [2]. CD4+ T cells expressing these specific TCRs recognize Tat peptides when they are processed and displayed by Human Leukocyte Antigen (HLA) class II molecules, typically HLA-DR or HLA-DQ [3]. This recognition triggers T-cell activation, leading to the secretion of pro-inflammatory cytokines like IFN-gamma and TNF-alpha, which help coordinate the broader immune response and can directly inhibit viral replication [4]. In the context of therapeutic development, these TCRs are being explored as templates for TCR-engineered T-cell therapies (TCR-T) and are the primary targets of therapeutic vaccines aimed at inducing robust cellular immunity to control the latent HIV reservoir [5]. However, the high genetic diversity of HIV-1 and the specific HLA requirements of these TCRs present significant challenges for universal clinical application [6]. Sources: [1] https://pubmed.ncbi.nlm.nih.gov/11752703/ [2] https://www.uniprot.org/uniprotkb/P04608/entry [3] https://pubmed.ncbi.nlm.nih.gov/15140914/ [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503271/ [5] https://clinicaltrials.gov/ct2/show/NCT00529659 [6] https://pubmed.ncbi.nlm.nih.gov/25122781/

Other names

HIV-1 Tat-specific T-cell receptorTat-specific CD4+ T-cell receptorMHC class II-restricted Tat-specific TCRCD4+ TCR recognizing Trans-Activator of Transcription peptides

Therapeutic vaccines aim to expand the endogenous population of CD4+ T cells expressing these TCRs to enhance viral control, while TCR-engineered T-cell therapies involve the adoptive transfer of T cells modified to express high-affinity TCRs that recognize Tat peptides presented by HLA class II on infected cells, leading to direct or indirect elimination of the viral reservoir.