HLA-E and HLA-E-Bound Peptides: Recognition by Subsets of NK and T Cells

Authors: Pietra, Gabriella; Romagnani, Chiara; Moretta, Lorenzo; Mingari, Maria C.

Source: Current Pharmaceutical Design, Volume 15, Number 28, October 2009 , pp. 3336-3344(9)

Publisher: Bentham Science Publishers

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Abstract:

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.

Keywords: HLA-E; natural killer cells; CD94/NKG2 receptors; human cytomegalovirus; gpUL40; ab TCR; alloreactivity; Graft-versus-host disease; graft rejection

Document Type: Research article

Affiliations: 1: Istituto Giannina Gaslini, Largo G. Gaslini, 516147 Genova, Italy.

Publication date: 2009-10-01

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Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

HLA-E and HLA-E-Bound Peptides: Recognition by Subsets of NK and T Cells

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