Human immunodeficiency virus 1 peptide-HLA-B*57 complex (HIV-p-HLA-B*57)

The Human immunodeficiency virus 1 peptide-HLA-B*57 complex is a specific peptide-major histocompatibility complex (pMHC) presented on the surface of HIV-infected cells, primarily CD4+ T cells. This complex is formed when intracellular HIV proteins, most notably the Gag polyprotein, are processed into short antigenic peptides (such as TW10 or KF11) and loaded onto the HLA-B*57 class I molecule for presentation to the immune system [1, 3]. HLA-B*57 is the most significant genetic host factor associated with the spontaneous control of HIV-1 replication, a phenotype observed in "elite controllers" [1]. The biological function of this complex is to serve as a signal for CD8+ cytotoxic T lymphocytes (CTLs) to recognize and destroy the infected cell [3]. In therapeutic development, this pMHC complex is utilized as a highly specific target for immunotherapies aimed at eradicating the HIV reservoir. Novel drug classes, such as Immune mobilizing monoclonal TCRs Against Virus (ImmTAVs) and TCR-engineered T cells (TCR-T), are engineered to bind this complex with much higher affinity than natural T-cell receptors [2, 4]. These agents facilitate the redirection of the immune system to kill infected cells that might otherwise evade detection through viral mutations or low antigen density [4]. While promising, these therapies are restricted to patients carrying the HLA-B*57 allele and carry risks of off-target cross-reactivity with similar self-peptides [2].

Other names

HLA-B*57-restricted HIV-1 antigenHIV-1 Gag peptide-HLA-B*57 complexpMHC complex (HIV/HLA-B*57)HIV-infected CD4+ T cells (HLA-B*57 restricted)

Redirection of T-cell cytotoxicity toward HIV-infected cells via high-affinity T-cell receptor (TCR) binding to the peptide-MHC complex.