Indirect recognition of donor HLA class I peptides in lung transplant recipients with bronchiolitis obliterans syndrome

Transplantation. 1999 Apr 27;67(8):1094-8. doi: 10.1097/00007890-199904270-00002.


Background: The presentation of donor MHC class II-derived peptides by host antigen-presenting cells in the context of self-MHC class II molecules has been suggested as a mechanism for the chronic rejection of kidney and heart allografts. The aim of this study was to determine whether indirect allorecognition of HLA class I-derived peptides occurred in lung transplant (LTx) recipients and whether it correlated with the development of bronchiolitis obliterans syndrome (BOS).

Methods: Peripheral blood mononuclear cells from LTx recipients were cultured with synthetic peptides corresponding to the hypervariable regions of the mismatched HLA class I antigens of the donor. Proliferation and precursor frequency (PF) of allopeptide reactive T cells were determined by the incorporation of [3H]thymidine into DNA and limiting dilution analysis.

Results: Peripheral blood leukocytes of LTx recipients with BOS mismatched for HLA class I molecules showed a proliferative response three- to fourfold higher than those observed in mismatched recipients without BOS and in normal control individuals (P<0.001). Similarly, the PF of allopeptide-reactive T cell was 3- to 24-fold higher in recipients with BOS compared with recipients without BOS (P<0.05) as well as normal control individuals (P<0.03). The T cell PF to donor-specific allopeptides, as well as irrelevant allopeptides, was not significantly different in LTx recipients without BOS and normal control individuals.

Conclusions: These data suggest that T cells from LTx recipients are sensitized to mismatched HLA class I antigens. The sensitization was significantly higher in LTx recipients with BOS compared with LTx recipients without BOS. Strategies to block T-cell responses generated by indirect allorecognition after lung transplantation may provide a means for the prevention or treatment of BOS in LTx recipients.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bronchiolitis Obliterans / immunology*
  • Cell Division / physiology
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Lung / immunology*
  • Lung Transplantation / immunology*
  • Postoperative Complications / immunology
  • Stem Cells / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • Tissue Donors*


  • Histocompatibility Antigens Class I