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
Current Pharmaceutical Design
Title: HLA-E and HLA-E-Bound Peptides: Recognition by Subsets of NK and T Cells
Volume: 15 Issue: 28
Author(s): Gabriella Pietra, Chiara Romagnani, Lorenzo Moretta and Maria Cristina Mingari
Affiliation:
Keywords: HLA-E, natural killer cells, CD94/NKG2 receptors, human cytomegalovirus, gpUL40, ab TCR, alloreactivity, Graft-versus-host disease, graft rejection
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.
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Cite this article as:
Pietra Gabriella, Romagnani Chiara, Moretta Lorenzo and Mingari Cristina Maria, HLA-E and HLA-E-Bound Peptides: Recognition by Subsets of NK and T Cells, Current Pharmaceutical Design 2009; 15 (28) . https://dx.doi.org/10.2174/138161209789105207
DOI https://dx.doi.org/10.2174/138161209789105207 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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