title: HLA-E regulates NKG2C+ natural killer cell function through presentation of a restricted peptide repertoire.
abstract: NK cells interact with the HLA-E molecule via the inhibitory receptor NKG2A and the activating receptor NKG2C. Hence, HLA-E can have a dual role in the immune response. In the present study, we aim to investigate the functional consequences of HLA-E for NKG2A and NKG2C expressing NK cell subsets by using a panel of HLA-E binding peptides derived from CMV, Hsp60 and HLA class I. PBMC derived from healthy subjects were used as targets for isolated NK cells and NK cell activation was examined by analysis of the expression of the degranulation marker CD107a. Peptide induced HLA-E expression inhibited degranulation of NKG2A+ NK cell subsets with almost all peptides, whereas NKG2A- NKG2C+ NK cell responses were enhanced only after incubation with four peptides; 1.3-fold with CMV(I), A80 and B13 and 3.2-fold with HLA-G derived peptide. In addition, the HLA-E:G peptide complex triggered NKG2C receptor internalization, as evidenced by reduction in the percentage of NKG2C+ NK cells when incubated with the peptide, which could be restored by addition of Bafilomycin.
  
  
  CONCLUSIONS
  in contrast to NKG2A, NKG2C is regulated by HLA-E only when HLA-E is in complex with a restricted peptide repertoire, especially in combination with the HLA-G leader peptide.
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Nina
authors.initials: N
authors.lastname: Lauterbach
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Lotte
authors.initials: L
authors.lastname: Wieten
authors.affiliation: NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Human Biology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Herman E
authors.initials: HE
authors.lastname: Popeijus
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Christina E M
authors.initials: CE
authors.lastname: Voorter
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: m.tilanus@mumc.nl.
authors.forename: Marcel G J
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology; D059951:HLA-G Antigens / Q000737:chemistry / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D000097625:HLA-E Antigens
chemical_list: D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D010455:Peptides; D000097625:HLA-E Antigens
keywords: HLA-E; NKG2A; NKG2C