Gillespie Geraldine M, Quastel Max N, McMichael Andrew J
Nuffield Department of Medicine, Center for Immuno-Oncology, University of Oxford, Oxford, UK.
Immunol Rev. 2025 Jan;329(1):e13434. doi: 10.1111/imr.13434.
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.
HLA - E是一种非经典、无多态性的Ib类HLA分子。其主要功能是将一种名为VL9的保守九肽（源自经典MHC分子的信号序列）呈递给自然杀伤细胞（NK细胞）和一部分T淋巴细胞表面的NKG2x - CD94受体。这些受体调节NK细胞的功能，这种在哺乳动物物种间保守的作用的重要性，可能解释了其缺乏基因多态性的原因。第二个次要功能是将其他与病原体相关的、结合较弱的肽呈递给T淋巴细胞。这些肽中的大多数与HLA - E的结合并不理想，但这种结合似乎是由无肽但具有反应性的HLA - E - β2m复合物的相对稳定性所促成的。反过来，这可能有利于与细菌感染细胞相关的非经典抗原加工。这篇综述探讨了与不同肽结合，然后与NKG2 - CD94或T细胞受体结合的HLA - E的结构，如何与HLA - E细胞生物学和免疫学相关。对该分子的详细了解可能为开发基于通用T细胞和NK细胞的免疫疗法带来机遇。
