title: Indirect allorecognition of mismatched donor HLA class II peptides in lung transplant recipients with bronchiolitis obliterans syndrome.
abstract: A correlation between indirect allorecognition of mismatched donor HLA class I peptides and development of bronchiolitis obliterans syndrome (BOS) after lung transplantation has been previously observed. The aim of this study was to determine whether there was a correlation between indirect allorecognition of mismatched donor HLA class II peptides and development of BOS after lung transplantation. Peripheral blood mononuclear cells from nine BOS+ and nine BOS-lung transplant recipients were cultured with synthetic peptides corresponding to the beta-chain hypervariable region of a mismatched donor HLA-DR molecule. Then, proliferative alloreactivity as well as frequency of alloreactive T cells were determined. In addition, the immunodominant epitopes from the donor HLA-DR molecules were identified in selected patients. T cells from BOS+ patients showed a dose-dependent proliferative alloreactivity against donor HLA-DR peptides that was significantly higher than that observed in BOS- patients (p=0.001). Similarly, the frequency of HLA-DR alloreactive T cells was significantly higher in BOS+ patients than in BOS- patients (p=0.001). This T-cell alloreactivity was directed against a single immunodominant HLA-DR peptide. These results suggest that indirect alloreactivity to donor HLA class II molecules may play a role in the pathogenesis of BOS after lung transplantation.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Reznik
authors.forename: A
authors.initials: A
authors.lastname: Jaramillo
authors.forename: K S
authors.initials: KS
authors.lastname: SivaSai
authors.forename: K L
authors.initials: KL
authors.lastname: Womer
authors.forename: M H
authors.initials: MH
authors.lastname: Sayegh
authors.forename: E P
authors.initials: EP
authors.lastname: Trulock
authors.forename: G A
authors.initials: GA
authors.lastname: Patterson
authors.forename: T
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000595:Amino Acid Sequence; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D005500:Follow-Up Studies; D006681:HLA-D Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000737:chemistry / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies; D010446:Peptide Fragments