LEUKOSIALIN (CD43) MAJOR HISTOCOMPATIBILITY CLASS-I MOLECULE INTERACTIONS INVOLVED IN SPONTANEOUS T-CELL CONJUGATE FORMATION

Resting T cells spontaneously adhere in a selective manner to potent a ccessory cells, such as dendritic cells (DC) and lymphoblastoid B blas ts (LCL). Here we demonstrate that leukosialin (CD43) and major histoc ompatibility complex class I molecules (MHC-I) might play a critical r ole in this process. T cell conjugate formation with monocyte-derived DC (md-DC) and LCL could be strongly inhibited by either preincubating T cells with Fab fragments of CD43 monoclonal antibody (mAb) 6F5 or b y preincubating md-DC or LCL with MHC-I mAb W6/32. Intact CD43 mAb 6F5 , in contrast to monovalent Fab fragments, enhanced T cell adhesivenes s by transactivating CD2 binding to CD58 molecules. Interestingly, ind uction of this proadhesive signal via CD43 with intact 6F5 mAb was fou nd to revert mAb W6/32-mediated inhibition of T cell conjugate formati on. These observations indicated that CD43 cross-linkage mimics and mo novalent mAb 6F5 inhibits interaction of T cell CD43 with a stimulator y ligand on opposing cells, presumably MHC-I. For the demonstration of direct physical interaction between CD43 on T cells and MHC-I-coated beads it was necessary, however, to ligate CD2 on T cells with a stimu latory pair of CD2 mAbs (VIT13 plus TS2/18). This suggests that CD2 li gation crosswise upregulates CD43 binding avidity for MHC-I and that b oth adhesion molecule pairs (CD43/MHC-I and CD2/CD58) act in concert t o induce and mediate T cell conjugate formation with certain cell type s.