HLA-E and HLA-E-bound peptides: Recognition by subsets of NK and T cells

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In humans, major histocompatibility complex (MHC) class I molecules comprise the classical (class Ia) human leukocyte antigens (HLA)-A, -B, and -C, and the non-classical (class Ib) HLA-E, -F, -G and -H (HFE) molecules. The best-characterized MHC class Ib molecule is HLA-E. HLA-E was first described as a non-polymorphic ligand of the CD94/NKG2 receptors expressed mainly by natural killer (NK) cells and its role was thus confined to the regulation of NK cell function. Therefore, interaction of HLA-E with the CD94/NKG2 receptors can result in either inhibition or activation of NK cells, depending on the peptide presented and on the NKG2 receptor CD94 is associated with. Thus, CD94/NKG2A functions as an inhibitory receptor, whereas CD94/NKG2C functions as an activating receptor. However, recent evidences obtained by our group and others indicated that HLA-E represents a novel restriction element for ab Tcell receptor (TCR)-mediated recognition. Although HLA-E displays a selective preference for nonameric peptides derived from the leader sequences of various HLA class I alleles, several reports showed that it can also present "noncanonical" peptides derived from both stress-related and pathogen-associated proteins. Because HLA-E displays binding specificity for innate CD94/NKG2 receptors but also has the features of an antigen-presenting molecule - including the ability to be recognized by ab T cells - it does appear that this MHC class Ib molecule plays an important role in both natural and acquired immune responses.

Original languageEnglish
Pages (from-to)3336-3344
Number of pages9
JournalCurrent Pharmaceutical Design
Issue number28
Publication statusPublished - Oct 2009


  • Ab TCR
  • Alloreactivity
  • CD94/NKG2 receptors
  • gpUL40
  • Graft rejection
  • Graft-versus-host disease
  • HLA-E
  • Human cytomegalovirus
  • Natural killer cells

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology


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