Indirect allorecognition of mismatched donor HLA class II peptides in lung transplant recipients with bronchiolitis obliterans syndrome.
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.
Reznik
S I
SI
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Jaramillo
A
A
SivaSai
K S
KS
Womer
K L
KL
Sayegh
M H
MH
Trulock
E P
EP
Patterson
G A
GA
Mohanakumar
T
T
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
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies; D010446:Peptide Fragments