HLA-E and HLA-E-bound peptides: recognition by subsets of NK and T cells.
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 T-cell 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 "non-canonical" 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.
Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Università degli Studi di Genova, 16132 Genova, Italy.
Gabriella
G
Pietra
Chiara
C
Romagnani
Lorenzo
L
Moretta
Maria Cristina
MC
Mingari
D000818:Animals; D006680:HLA Antigens / Q000737:chemistry*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry*; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D000097625:HLA-E Antigens
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides; D000097625:HLA-E Antigens