HIV-1 Gag peptide–HLA-A*02:01 complex (Gag-HLA-A*02:01)

The HIV-1 Gag peptide–HLA-A*02:01 complex is a molecular assembly consisting of a specific immunodominant peptide derived from the HIV-1 Gag protein, typically the SL9 epitope (SLYNTVATL), bound to the Human Leukocyte Antigen (HLA) A*02:01 molecule (PMID: 10590268). This complex is presented on the surface of HIV-infected cells, serving as a critical signal for recognition by the cellular immune system, specifically CD8+ cytotoxic T lymphocytes (PMID: 21107318). In the context of therapeutic development, this peptide-MHC (pMHC) complex is a primary target for immunotherapies such as TCR-engineered T cells and bispecific T-cell engagers, like ImmTAV molecules, designed to eliminate the HIV reservoir (Immunocore, 2023). By specifically binding to this complex, these therapies aim to redirect the immune system to identify and destroy cells harboring the virus, even during antiretroviral therapy. However, the high mutation rate of HIV can lead to epitope escape, and potential cross-reactivity with similar human peptides remains a significant safety consideration in drug design (PMID: 30206131). The complex is a hallmark of the immune response in HLA-A*02:01 positive individuals, and successful targeting could lead to a functional cure by depleting the latent HIV reservoir.

Other names

SLYNTVATL-HLA-A*02:01 complexHIV-1 Gag p17 (77-85) peptide-MHC complexGag SL9-HLA-A*02:01pMHC complex (Gag-SL9/HLA-A*02:01)

T-cell receptor (TCR) mediated recognition and subsequent activation of cytotoxic T-lymphocyte effector functions against cells presenting the viral peptide.