XXXX activation epitopes induced by leukocyte activation.

@entity1 @entity19466 @entity1454 @entity1453 @entity2071
The cell surface adhesion molecule @entity1453 coordinates leukocyte trafficking and is a costimulatory molecule for T cell activation. We developed a panel of mAbs that recognize activation epitopes on the @entity1454 subunit, and show that stimulation of T lymphocytes appears to be accompanied by a conformational change in a subpopulation of @entity1453 that does not require ligand binding. Activation epitope up-regulation requires divalent cations, is sensitive to cellular signal transduction events, and correlates with cell adhesion. In addition, the stimulated appearance of these activation epitopes is absent in cell lines from @entity1 with leukocyte adhesion deficiency-1/variant that has previously been shown to be defective in @entity1453 activation. Thus, these activation epitope Abs can be used to dissect signal transmission to @entity1454 . Evidence suggests that these @entity1454 activation epitopes are induced early in cellular activation and are independent of actin rearrangement necessary for avid adhesion. We have also determined that function-blocking @entity1454 Abs inhibit the induction of activation epitopes. One activation epitope Ab binds to a site on @entity1454 distinct from that of the blocking Abs, indicating that the blocking Abs suppress a conformational change in @entity1453 . We also find that these neoepitopes are present on @entity19466 with high affinity for @entity2071 and their binding is modulated in parallel with the affinity of @entity1453 for @entity2071 . Collectively, these neoepitope Abs identify a subpopulation of @entity1453 most likely with high affinity for @entity2071 and necessary for @entity1453 function.
