title: Isolation of human CD4/CD8 double-positive, graft-versus-host disease-protective, minor histocompatibility antigen-specific regulatory T cells and of a novel HLA-DR7-restricted HY-specific CD4 clone.
abstract: Minor histocompatibility (H) Ags are classically described as self-peptides derived from intracellular proteins that are expressed at the cell surface by MHC class I and class II molecules and that induce T cell alloresponses. We have isolated three different T cell populations from a skin biopsy of a patient suffering from acute graft-versus-host disease following sex-mismatched HLA-identical bone marrow transplantation. The first population was: 1) CD4(+)/CD8(+) double-positive; 2) specific for an HLA class I-restricted autosomal Ag; 3) expressed a Tr1 profile with high levels of IL-10, but low IL-2 and IFN-γ; and 4) exerted regulatory function in the presence of recipient APCs. The second was CD8 positive, specific for an HLA class I-restricted autosomally encoded minor H Ag, but was only weakly cytotoxic. The third was CD4 single positive, specific for an HLA-DR7-restricted HY epitope and exerted both proliferative and cytotoxic functions. Identification of the peptide recognized by these latter cells revealed a new human HY epitope, TGKIINFIKFDTGNL, encoded by RPS4Y and restricted by HLA-DR7. In this paper, we show human CD4/CD8 double-positive, acute graft-versus-host disease-protective, minor H Ag-specific regulatory T cells and identify a novel HLA-DR7/ HY T cell epitope, encoded by RPS4Y, a potential new therapeutic target.
authors.affiliation: Etablissement Français du Sang Rhone Alpes, HLA Department, Lyon 69007, France. assia.eljaafari@univ-lyon1.fr
authors.forename: Assia
authors.initials: A
authors.lastname: Eljaafari
authors.forename: Ozel
authors.initials: O
authors.lastname: Yuruker
authors.forename: Christophe
authors.initials: C
authors.lastname: Ferrand
authors.forename: Annie
authors.initials: A
authors.lastname: Farre
authors.forename: Caroline
authors.initials: C
authors.lastname: Addey
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Tartelin
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Pierre
authors.initials: P
authors.lastname: Tiberghien
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Simpson
authors.forename: Dominique
authors.initials: D
authors.lastname: Rigal
authors.forename: Diane
authors.initials: D
authors.lastname: Scott
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002461:Cell Line, Transformed; D002469:Cell Separation / Q000379:methods; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006182:H-Y Antigen / Q000276:immunology*; D015809:HLA-DR7 Antigen / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D006182:H-Y Antigen; D015809:HLA-DR7 Antigen; D059811:HLA-DRB1 Chains; D015778:Minor Histocompatibility Antigens