HLA class I: an unexpected role in integrin β4 signaling in endothelial cells.
The production of anti-donor antibodies to HLA class I and class II antigens following transplantation is associated with development of transplant vasculopathy and graft loss. Antibodies against HLA class I (HLA-I) molecules are thought to contribute to transplant vasculopathy by triggering signals that elicit the activation and proliferation of endothelial cells. The proximal molecular events that regulate HLA-I dependent signal transduction are not well understood. We demonstrated a mutual dependency between HLA-I and integrin β4 to stimulate signal transduction and cell proliferation. Similarly, we found that integrin β4-mediated cell migration was dependent upon its interactions with HLA-I molecules. Since integrin β4 has been implicated in angiogenesis and tumor formation, associations between integrin β4 and HLA-I may play an important role in cancer. Further characterization of interactions between HLA-I and integrin β4 may lead to the development of therapeutic strategies for the treatment and prevention of chronic allograft rejection and cancer.
UCLA Immunogenetics Center, Department of Pathology, David Geffen School of Medicine, University of California, 1000 Veteran Ave., Los Angeles, CA 90095, United States. xiaozhang@mednet.ucla.edu
Xiaohai
X
Zhang
Elaine F
EF
Reed
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D039663:Integrin beta4