Abstract
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.
Highlights
Major histocompatibility complex (MHC) class I molecules may be subdivided into two families, MHC class Ia and MHC class Ib
The T-cell recognition of murine MHC class Ib molecules was described over a decade ago, the ability of human Human leukocyte antigen (HLA) class Ib molecules to stimulate T-cell responses is only being recognized
It is still unclear whether HLA-F and -G are involved in stimulating CD8+ T cells
Summary
Major histocompatibility complex (MHC) class I molecules may be subdivided into two families, MHC class Ia (classical) and MHC class Ib (nonclassical). Cell surface expression of HLA-E depends on binding of nonamer peptides derived from the signal sequence of MHC class I molecules [7]. HLA-E was first described as the ligand for CD94/NKG2A (inhibitory) and CD94/NKG2C (activating) NK receptors [13,14,15], mainly confining its regulatory function to NK cell population, emerging evidence (obtained by our and other groups) clearly support the notion that HLA-E can serve as a restricting element for the TCR of some αβ T cells [16,17,18,19,20] Along this line, this MHC class Ib molecule plays an important role in both natural and acquired immune responses [21]
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