Human leukocyte antigen class I histocompatibility antigen, alpha chain E (HLA-E)

Human leukocyte antigen class I histocompatibility antigen, alpha chain E (HLA-E) is a non-classical MHC class Ib molecule that plays a pivotal role in regulating the immune system [UniProt P13747]. Unlike classical MHC molecules, HLA-E displays limited polymorphism and primarily presents peptides derived from the signal sequences of other HLA class I molecules [Borst et al., 2020]. Its primary biological function is to act as a ligand for the heterodimeric inhibitory receptor CD94/NKG2A, which is expressed on natural killer (NK) cells and a subset of CD8+ T cells [Kamiya et al., 2019]. Upon binding to NKG2A, HLA-E triggers an inhibitory signal that prevents immune cell-mediated lysis, thereby maintaining self-tolerance [PubMed: 32071424]. In the context of oncology, many tumors upregulate HLA-E to evade immune detection and destruction, making it a significant immune checkpoint [Nature Reviews Immunology, 2020]. Therapeutic interventions, such as the monoclonal antibody monalizumab, target this axis by preventing the HLA-E/NKG2A interaction to restore anti-tumor immune responses [ClinicalTrials.gov: NCT02671435]. Beyond cancer, HLA-E is involved in the immune response to viral infections, such as cytomegalovirus, and has implications in maternal-fetal tolerance [NCBI Gene: 3133].

Other names

HLA-6.2MHC class I antigen EHLAEHLA-E

Blockade of the HLA-E/NKG2A inhibitory signaling pathway to enhance anti-tumor immunity.