ANTI-HLA ANTIBODY LIGATION TO HLA CLASS-I MOLECULES EXPRESSED BY ENDOTHELIAL-CELLS STIMULATES TYROSINE PHOSPHORYLATION, INOSITOL PHOSPHATE GENERATION, AND PROLIFERATION

The major threat to long-term survival of solid organ allografts is ch ronic rejection. Progressive narrowing and ultimate luminal occlusion of the arteries and arterioles of the transplanted organ are the hallm arks of the disease. The mechanism of chronic rejection is poorly unde rstood, but it is suspected that the associated vascular changes are a result of anti-HLA antibody-mediated injury to the endothelium. We ha ve postulated that anti-HLA antibodies initiate chronic rejection by b inding to class I molecules on the endothelium and transducing signals that result in endothelial cell activation and proliferation. Our dat a demonstrate that anti-HLA class I antibodies transduce signals in en dothelial cells stimulating increased tyrosine phosphorylation of intr acellular proteins. Antibody binding to class I antigens also leads to the generation of inositol phosphate and endothelial cell proliferati on. These results indicate that anti-KLA antibodies can deliver functi onally important signals to endothelial cells, a finding that may be f undamental to an understanding of the mechanisms of chronic rejection. (C) American Society for Histocompatibility and Immunogenetics, 1997.