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Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecules (ICAMs) facilitates T cell antigen receptor (TCR)-mediated killing. To dissect TCR and LFA-1 contributions, we evaluated cytolytic activity and granule release by cytotoxic T lymphocytes (CTL) as well as intracellular granule redistribution and morphology of CTL stimulated with natural TCR ligand in the presence or absence of LFA-1 engagement. Although other adhesion mechanisms, e.g., CD2-CD58 interaction, could substitute for LFA-1 to trigger CTL degranulation, productive LFA-1 ligation was indispensable for effective target cell lysis by the released granules. LFA-1-mediated adhesion to glass-supported bilayers containing intercellular adhesion molecule-1 was characterized by a much larger junction area, marked by LFA-1 segregation, and a more compact cell shape compared with those observed for CD2-mediated adhesion to bilayers containing CD58. A larger contact induced by intercellular adhesion molecule 1 determined a unique positioning of granules near the interface. These data provide evidence that LFA-1 delivers a distinct signal essential for directing released cytolytic granules to the surface of antigen-bearing target cells to mediate the effective destruction of these cells by CTL.

Original publication

DOI

10.1073/pnas.0502467102

Type

Journal article

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Date

05/2005

Volume

102

Pages

6437 - 6442

Addresses

Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Keywords

T-Lymphocytes, Cytotoxic, Cell Line, Hybridomas, Secretory Vesicles, Humans, Cell Adhesion Molecules, Lymphocyte Function-Associated Antigen-1, Receptors, Antigen, T-Cell, HLA-A2 Antigen, Cytotoxicity Tests, Immunologic, Fluorescent Antibody Technique, Cell Adhesion, Signal Transduction, Cytotoxicity, Immunologic