CONTRIBUTION LYMPHOCYTE FUNCTION-ASSOCIATED-1 INTERCELLULAR ADHESION MOLECULE-1 BINDING TO THE ADHESION SIGNALING CASCADE OF CYTOTOXIC T-LYMPHOCYTE ACTIVATION/

A rapid induction of adhesion to immobilized intercellular adhesion mo lecule (ICAM)-1 occurs when cytotoxic T lymphocytes (CTL) are stimulat ed with either soluble anti-T cell receptor (TCR) monoclonal antibodie s (mAb) or with immobilized alloantigen, and this binding is blocked b y the addition of anti-lymphocyte function-associated (LFA)-1 mAbs. Re quirements for activating LFA-1 adhesion to ICAM-1 are similar to thos e found for induction of binding to immobilized firbronectin (FN), but distinct from those for activating CD8-mediated adhesion to class I m ajor histocompatibility complex. A distinct role for LFA-1 in co-signa ling for TCR-dependent degranulation could not be demonstrated. In con trast, both CD8 and the FN-binding integrin provide costimulatory sign als for this response. Thus, if co-signaling via LFA-1 occurs, it clea rly differs from that provided by CD8 or the FN-binding integrin. On t he basis of antibody blocking effects, alloantigen-dependent activatio n of adhesion to ICAM-1 involves both the TCR and CD8. These results s upport a view of CTL activation as a cascade of adhesion and signaling events, with different coreceptors making distinct contributions.