HLA-E: immune receptor functional mechanisms revealed by structural studies

Journal article : Review

HLA-E is a nonclassical, nonpolymorphic, class Ib HLA molecule. Its primary function is to present a conserved nonamer peptide, termed VL9, derived from the signal sequence of classical MHC molecules to the NKG2x-CD94 receptors on NK cells and a subset of T lymphocytes. These receptors regulate the function of NK cells, and the importance of this role, which is conserved across mammalian species, probably accounts for the lack of genetic polymorphism. A second minor function is to present other, weaker binding, pathogen-derived peptides to T lymphocytes. Most of these peptides bind suboptimally to HLA-E, but this binding appears to be enabled by the relative stability of peptide-free, but receptive, HLA-E-β2m complexes. This, in turn, may favor nonclassical antigen processing that may be associated with bacteria infected cells. This review explores how the structure of HLA-E, bound to different peptides and then to NKG2-CD94 or T-cell receptors, relates to HLA-E cell biology and immunology. A detailed understanding of this molecule could open up opportunities for development of universal T-cell and NK-cell-based immunotherapies.

Authors: Gillespie, GM; Quastel, MN; McMichael, AJ

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Immunological Reviews
• Volume: 329
• Issue: 1
• Article number: e13434
• Place of publication: England
• Publication date: 2025-01-03
• Acceptance date: 2024-12-10
• DOI: 10.1111/imr.13434
• EISSN: 1600-065X
• ISSN: 0105-2896
• Pmid: 39753525
• Language: English
• Keywords: T-cell receptors; CD8 T cells; HLA-E; MHC class I; MHC-E; NKG2A
• Subtype: Review