Structural requirements for CD43 function

The regulation of T cell activation and adhesion by CD43 (leukosialin, sial ophorin) has been thought to be mainly a function of the large size and neg ative charge of the extracellular domain of the protein. In this work, we d emonstrate that the cytoplasmic tail is both necessary and sufficient for t he negative regulatory effect of CD43 on cell-cell adhesion. Expression of mutant CD43 proteins in primary T cells from CD43-deficient mice demonstrat ed that the antiproliferative effect of CD43 is also dependent upon the cyt oplasmic tail. In contrast, Ab-mediated costimulation through CD43 does not require the intracellular domain of CD43, These data demonstrate that CD43 primarily serves as a negative regulator of T cell activation and adhesion , and that this is mediated not exclusively by passive effects of the extra cellular domain, but requires participation of the cytoplasmic tail, perhap s through interactions with the cytoskeleton, or alternatively, active regu lation of intracellular signaling pathways.