title: Chronic graft versus host disease is associated with an immune response to autologous human leukocyte antigen-derived peptides.
abstract: BACKGROUND
  Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic bone marrow transplantation (BMT) the immunopathogenesis of which is not well understood. Humoral and cellular immunity are both implicated, patients express a range of autoantibodies, but the targets of cellular immunity are not well defined. Autologous human leukocyte antigen (HLA)-derived peptides constitute a significant proportion of the repertoire.
  
  
  METHODS
  We have investigated the response to HLA-derived peptides after allogeneic BMT using gamma-interferon enzyme-linked immunospot assay (ELISPOT). We also studied the release of this gamma-interferon by flow cytometry in a subgroup of responsive patients.
  
  
  RESULTS
  The peripheral blood mononuclear cell response was assessed by gamma-interferon ELISPOT in 42 BMT recipients (21 with cGVHD) and 30 healthy donors. Thirteen of 21 patients diagnosed with cGVHD responded to at least one HLA-derived peptide compared with 1 of 21 patients without cGVHD (62% vs. 5%, P<10) and 1 of 30 healthy donors. In all but one patient these peptides correspond with the sequences of autologous HLA. The median single peptide-specific response in ELISPOT was 43/10 peripheral blood mononuclear cells. In a subgroup studied by flow cytometry, gamma-interferon production to individual peptides occurred in 0.04% to 0.18% of CD4 T lymphocytes.
  
  
  CONCLUSIONS
  These observations identify HLA-derived peptides as targets of a cellular immune response in cGVHD.
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, UK & School of Immunity, Infection and Inflammation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Smith
authors.forename: Rajesh
authors.initials: R
authors.lastname: Hanvesakul
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Morgan
authors.forename: Andrew
authors.initials: A
authors.lastname: Bentall
authors.forename: David
authors.initials: D
authors.lastname: Briggs
authors.forename: Fiona
authors.initials: F
authors.lastname: Clark
authors.forename: Guy
authors.initials: G
authors.lastname: Pratt
authors.forename: Paul
authors.initials: P
authors.lastname: Moss
authors.forename: Mark
authors.initials: M
authors.lastname: Larché
authors.forename: Simon
authors.initials: S
authors.lastname: Ball
mesh_terms: D016026:Bone Marrow Transplantation / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D016130:Immunophenotyping / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007938:Leukemia / Q000601:surgery; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma