Antigen-receptor complex stimulation triggers protein kinase C-dependent CD11a/CD18-cytoskeleton association in T lymphocytes.
Although it is well accepted that intercellular adhesion involving the CD11a/CD18 (LFA-1) complex is critical in a wide array of T cell-dependent processes, recent demonstrations of an LFA-1 high avidity state, induced by triggering the T cell receptor (TCR) complex, has raised questions about the intracellular signals generated and molecular events leading to effective cell coupling, as well as their orderly sequence. In this study, we assessed the effects of T cell activation on the actin-based cytoskeleton, and LFA-1, as well as their interaction. Crosslinking the TCR complex with anti-CD3 mAb resulted in actin polymerization and colocalization with LFA-1, as detected by fluorescence microscopy. This association was confirmed by immunoprecipitating LFA-1 from the detergent insoluble, cytoskeletal-associated membrane fraction after TCR crosslinking. These consequences were inhibited by the protein kinase C (PKC) inhibitor staurosporine or by PKC desensitization, as was a transient CD11a hyperphosphorylation, induced by monoclonal anti-CD3. Furthermore, a small percentage of beta 2-deficient T cells maintained the ability to rearrange the cytoskeleton in response to TCR complex activation, with F-actin-VLA4 colocalization. These results provide evidence that the important consequences of TCR-induced signal transduction include a PKC-dependent cytoskeletal rearrangement, involving an association between leukocyte integrins and F-actin. We discuss the implications of these findings with respect to effective T cell functions.
Scientific Institute S. Raffaele, Milan, Italy.
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Pardi
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Inverardi
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C
Rugarli
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JR
Bender
D000199:Actins / Q000032:analysis; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018821:CD18 Antigens; D017252:CD3 Complex; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000648:ultrastructure; D003599:Cytoskeleton / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D006801:Humans; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects* / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000199:Actins; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018821:CD18 Antigens; D017252:CD3 Complex; D003598:Cytoskeletal Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D011493:Protein Kinase C