Sci. Signal., 23 November 2010
Integrating RejectionHuman leukocyte antigens (HLAs), major histocompatibility complexes in humans, are best known for presenting antigens to immune cells; however, they also mediate other processes. For example, antibody-mediated cross-linking of HLA class I (HLA-I) on the surface of endothelial cells triggers proliferation, involving the activation of the kinases PI3K, Akt, and ERK. HLA-I molecules have no kinase activity, so it is thought that they must associate with other proteins to mediate such signaling. In the context of organ transplantation, the development of recipient antibodies against donor HLA molecules leads to an increased risk of tissue rejection, which is associated with endothelial cell proliferation and migration. Zhang et al. found that cross-linking with antibody against HLA-I triggered a physical and functional association between HLA-I and the integrin β4 subunit in human endothelial cells. Knockdown of HLA-I impaired integrin β4 signaling and the migration of endothelial cells, whereas knockdown of integrin β4 prevented the proliferation of cells in response to antibody-induced cross-linking of HLA-I. Discovery of the interaction between integrin β4 and HLA-I may lead to the development of therapeutic strategies to prevent antibody-mediated transplant rejection and other pathologies.
Citation: X. Zhang, E. Rozengurt, E. F. Reed, HLA Class I Molecules Partner with Integrin β4 to Stimulate Endothelial Cell Proliferation and Migration. Sci. Signal. 3, ra85 (2010).
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