Contribution of 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 molecule (ICAM)-1 occurs when cytotoxic T lymphocytes (CTL) are stimulated with either soluble anti-T cell receptor (TCR) monoclonal antibodies (mAb) or with immobilized alloantigen, and this binding is blocked by the addition of anti-lymphocyte function-associated (LFA)-1 mAbs. Requirements for activating LFA-1 adhesion to ICAM-1 are similar to those found for induction of binding to immobilized fibronectin (FN), but distinct from those for activating CD8-mediated adhesion to class I major histocompatibility complex. A distinct role for LFA-1 in co-signaling for TCR-dependent degranulation could not be demonstrated. In contrast, both CD8 and the FN-binding integrin provide costimulatory signals for this response. Thus, if co-signaling via LFA-1 occurs, it clearly differs from that provided by CD8 or the FN-binding integrin. On the basis of antibody blocking effects, alloantigen-dependent activation of adhesion to ICAM-1 involves both the TCR and CD8. These results support a view of CTL activation as a cascade of adhesion and signaling events, with different coreceptors making distinct contributions.
Ybarrondo
B
B
Division of Membrane Biology, Medical Biology Institute, La Jolla, California 92037.
O'Rourke
A M
AM
Brian
A A
AA
Mescher
M F
MF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D018799:Intercellular Adhesion Molecule-1; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1