MURINE CD4(-CELLS UNDERGO TCR-ACTIVATED ADHESION TO EXTRACELLULAR-MATRIX PROTEINS BUT NOT TO NONANTIGENIC MHC CLASS-II PROTEINS() T)

Engagement of the TCR modulates the avidity of several receptors that play key roles in lymphocyte adhesion and/or signal transduction, incl uding CD8, CD11a/CD18 (LFA-1), CD2, and several beta 1-integrins. Here , we investigated whether CD4(+) T cells similarly undergo TCR-regulat ed adhesion to isolated MHC class II proteins through CD4. Strong adhe sion of a number of CD4(+) T cell clones to immobilized antigenic pept ide/class II complexes was readily detectable. Adhesion to antigenic c lass II proteins was CD4; dependent and inhibited by pretreatment of T cells with the protein tyrosine kinase inhibitor herbimycin A, sugges ting that adhesion requires TCR- and/or CD4-derived signal transductio n. Treatment of T cells with anti-TCR Ab strongly increased subsequent adhesion to the extracellular matrix proteins, fibronectin and vitron ectin, but, significantly, not to immobilized nonantigenic class II pr oteins. Suboptimal densities of antigenic peptide/class II complexes a lso activated,adhesion of T cells to coimmobilized fibronectin or vitr onectin, and this resulted in production of IFN-gamma to levels exceed ing those stimulated by optimal densities of antigenic class II comple xes 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, su ggest fundamental differences in the mechanism by which the TCR regula tes coreceptor adhesion in CD4(+) and CD8(+) T cells.