HIV Gag-derived peptide–HLA-E complex (HIV Gag–HLA-E)

The HIV Gag-derived peptide–HLA-E complex is a molecular assembly where a peptide fragment from the HIV-1 Gag protein is presented by the non-classical Major Histocompatibility Complex (MHC) class Ib molecule, HLA-E (Hansen et al., 2016, Science). In a typical immune environment, HLA-E primarily presents highly conserved leader peptides from other MHC class I molecules to interact with inhibitory receptors on Natural Killer (NK) cells, such as NKG2A, to maintain self-tolerance (Borst et al., 2020, Nature Reviews Immunology). However, research into Cytomegalovirus (CMV)-vectored vaccines has demonstrated that HLA-E can be programmed to present unconventional viral peptides, such as those derived from the HIV Gag protein, to CD8+ T cells (Picker et al., 2013, Nature). This complex is a significant therapeutic target because HLA-E-restricted T cells can recognize HIV-infected cells even when the virus has downregulated classical MHC class I molecules to evade the immune system (Yang et al., 2021, Journal of Virology). The most notable therapeutic approach targeting this complex is the development of CMV-based vaccine vectors, such as VIR-1111, which aim to elicit a broad and persistent T-cell response (Vir Biotechnology, 2021). Understanding the structural and immunological properties of the Gag–HLA-E complex is essential for designing next-generation immunotherapies and vaccines intended to achieve functional cure or prevention of HIV infection.

Other names

HIV Gag peptide-HLA-E complexHLA-E/HIV Gag complexMHC class Ib-peptide complex

Induction of HLA-E-restricted CD8+ T cell responses to recognize and eliminate HIV-infected cells.