Human immunodeficiency virus type 1 Negative regulatory factor peptide-Major histocompatibility complex (HIV-1 Nef pMHC)

Human immunodeficiency virus type 1 (HIV-1) Negative regulatory factor (Nef) is a 27-35 kDa myristoylated accessory protein essential for high-titer viral replication and the progression to AIDS [UniProt: P03406]. Nef functions primarily as a virulence factor by downregulating cell surface molecules such as CD4 and Major Histocompatibility Complex class I (MHC-I), which allows the virus to evade detection by cytotoxic T lymphocytes [PubMed: 28834711]. Despite this downregulation, specific Nef-derived peptides are processed and presented by the remaining MHC-I molecules on the surface of infected cells. These peptide-MHC (pMHC) complexes serve as highly specific targets for engineered T-cell receptors (TCRs) in the context of adoptive cell transfer or soluble TCR immunotherapies [PubMed: 30249038]. By targeting these complexes, the immune system can be redirected to identify and eliminate HIV-infected cells, including those within the latent reservoir [PubMed: 33106571]. However, the effectiveness of this approach is limited by the high mutational rate of HIV, which can lead to epitope escape, and the requirement for specific HLA alleles in the patient population [PubMed: 25605868].

Other names

HIV-1 Nef antigenNef-HLA complexNef peptide-MHC complexHIV-1 Nef p/MHCNef-HLA-A*02:01

Engineered T-cell receptors (TCRs) or soluble TCR-based molecules bind specifically to HIV-1 Nef-derived peptides presented by Major Histocompatibility Complex (MHC) class I molecules on the surface of infected cells, triggering cytotoxic T-lymphocyte activation and subsequent cell lysis [PubMed: 30249038].