ROLE OF ADHESION MOLECULES IN THE MECHANISM OF NON-MHC (MAJOR HISTOCOMPATIBILITY COMPLEX) RESTRICTED CELL-MEDIATED CYTOTOXICITY

Adhesion molecules involved in the interaction between immune system e ffector cells and tumor targets are surface molecules which contribute to the formation of cell-to-cell contacts and belong to the integrin family. In this paper, the role played by the adhesion molecules in th e process of cell-mediated cytotoxicity is reviewed. Furthermore, the contact area between effector and target cells has been analyzed by sc anning electron microscopy. This region, termed ''closed chamber'', se ems to contribute to killing efficiency by creating an intimate contac t region in which cytotoxic factors can easily induce lethal hit in ta rget cell. Thus, the extension of the closed chamber seems to be posit ively related to effector cell killing potential as well as to target cell sensitivity and, in this context, the adhesion molecules prove to play a pivotal role. In fact, a receptor-ligand interaction occurs be tween CD11a/CD18 (LFA-1) and CD2 molecules, expressed on the effector cells, and the respective counterparts on target cells, i.e., ICAM-1, ICAM-2, or LFA-3. Treatment with antibodies against such molecules str ongly modifies closed chamber formation without inhibiting cell-to-cel l binding. Nevertheless, in these conditions, the killing ability of d ifferent effector cells toward tumor targets appears to be strongly im paired. Hence, the adhesion molecules seem to be strongly involved in the formation of the closed chamber as well as in the activation of ef fector cell killing machinery.