title: Antibodies to HLA Molecules Mimic Agonistic Stimulation to Trigger Vascular Cell Changes and Induce Allograft Injury.
abstract: Human leukocyte antigen (HLA)-induced signaling in endothelial and smooth muscle cells causes dramatic cytoskeletal rearrangement, increased survival, motility, proliferation, adhesion molecule and chemokine expression, and adhesion of leukocytes. These mechanisms are directly related to endothelial activation, neointimal proliferation, and intragraft accumulation of leukocytes during antibody-mediated rejection (AMR) and chronic rejection. Clustering of HLA by ligands intrans, such as in antigen-presenting cells at the immune synapse, triggers physiological functions analogous to HLA antibody-induced signaling in vascular cells. Emerging evidence has revealed previously unknown functions for HLA beyond antigen presentation, including association with coreceptors incisto permit signal transduction, and modulation of intracellular signaling downstream of other receptors that may be relevant to HLA signaling in the graft vasculature. We discuss the literature regarding HLA-induced signaling in vascular endothelial and smooth muscle cells, as well as under endogenous biological conditions, and how such signaling relates to functional changes and pathological mechanisms during graft injury.
authors.affiliation: UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, 1000 Veteran Ave Room 1-520, Los Angeles, CA 90095, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Valenzuela
authors.affiliation: UCLA Immunogenetics Center, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, 1000 Veteran Ave Room 1-520, Los Angeles, CA 90095, USA.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
keywords: Antibody-mediated rejection; Endothelial cells; HLA antibodies; Leukocyte recruitment; Mammalian target of rapamycin (mTOR); Signal transduction