Murine CD4+ T cells undergo TCR-activated adhesion to extracellular matrix proteins but not to nonantigenic MHC class II proteins.
Engagement of the TCR modulates the avidity of several receptors that play key roles in lymphocyte adhesion and/or signal transduction, including CD8, CD11a/CD18 (LFA-1), CD2, and several beta 1-integrins. Here, we investigated whether CD4+ T cells similarly undergo TCR-regulated adhesion to isolated MHC class II proteins through CD4. Strong adhesion of a number of CD4+ T cell clones to immobilized antigenic peptide/class II complexes was readily detectable. Adhesion to antigenic class II proteins was CD4 dependent and inhibited by pretreatment of T cells with the protein tyrosine kinase inhibitor herbimycin A, suggesting that adhesion requires TCR- and/or CD4-derived signal transduction. Treatment of T cells with anti-TCR Ab strongly increased subsequent adhesion to the extracellular matrix proteins, fibronectin and vitronectin, but, significantly, not to immobilized nonantigenic class II proteins. Suboptimal densities of antigenic peptide/class II complexes also activated adhesion of T cells to coimmobilized fibronectin or vitronectin, and this resulted in production of IFN-gamma to levels exceeding those stimulated by optimal densities of antigenic class II complexes alone. However, no augmentation of adhesion or cytokine secretion occurred when self or third party class II proteins were coimmobilized with antigenic class II complexes. The present results, therefore, suggest fundamental differences in the mechanism by which the TCR regulates coreceptor adhesion in CD4+ and CD8+ T cells.
O'Rourke
A M
AM
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Lasam
M C
MC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology*; D002999:Clone Cells; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007424:Intracellular Fluid / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell