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 β‐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.