The Emerging Role of HLA-E-Restricted CD8+ T Lymphocytes in the Adaptive Immune Response to Pathogens and Tumors

Abstract EN

Human leukocyte antigen (HLA)-E is a nonclassical major histocompatibility complex (MHC) class I molecule of limited sequence variability that is expressed by most tissues albeit at low levels.

HLA-E has been first described as the ligand of CD94/NKG2 receptors expressed mainly by natural killer (NK) cells, thus confining its role to the regulation of NK-cell function.

However, recent evidences obtained by our and other groups indicate that HLA-E complexed with peptides can interact with αβ T-cell receptor (TCR) expressed on CD8+ T cells.

Although, HLA-E displays a selective preference for nonameric peptides, derived from the leader sequence of various HLA class I alleles, several reports indicate that it can present also “noncanonical” peptides derived from both stress-related and pathogen-associated proteins.

Because HLA-E displays binding specificity for innate CD94/NKG2 receptors, as well as all the features of an antigen-presenting molecule, its role in both natural and acquired immune responses has recently been re-evaluated.