HIV-1 Negative Factor (Nef) peptides presented on Major Histocompatibility Complex (MHC) class I (HIV Nef-pMHC-I)

HIV-1 Negative Factor (Nef) is a 27-34 kDa accessory protein essential for high-level viral replication and the progression to AIDS (UniProt P03406). It is expressed early in the viral life cycle and plays a pivotal role in immune evasion by downregulating cell-surface Major Histocompatibility Complex class I (MHC-I) molecules, which prevents the recognition of infected cells by cytotoxic T lymphocytes (Collins et al., Nature, 1998). Despite this downregulation, specific Nef-derived peptides are processed and presented on the remaining MHC-I molecules, serving as highly specific markers for HIV-infected cells (HIV Molecular Immunology Database). These peptide-MHC (pMHC) complexes are currently being explored as therapeutic targets for T-cell receptor (TCR) engineered T cells and bispecific T-cell engagers designed to eliminate the latent HIV reservoir (Specht et al., Current Opinion in HIV and AIDS, 2020). The primary therapeutic challenge involves the high mutational rate of the Nef protein and the significant polymorphism of HLA alleles across different human populations. Targeting these complexes aims to provide a precision medicine approach to achieving a functional cure for HIV infection by bypassing the virus's natural evasion mechanisms.

Other names

HIV Nef-HLA complexNef-derived epitope-MHC class I complexHIV-1 Nef peptide-HLA-A*02:01Nef-pMHCHIV-1 Nef-derived peptide-HLA-B*07:02 complex

Targeting of specific Nef-derived peptide-MHC complexes by engineered T-cell receptors or bispecific molecules to induce cytotoxic T-lymphocyte (CTL) mediated lysis of HIV-infected cells and reduce the viral reservoir.