Augmentation of mature CD4+ T cell responses to isolated antigenic class II proteins by fibronectin and intercellular...

Mature CD4+ T cells can undergo stable adhesion to isolated antigenic MHC complexes, and upon TCR engagement exhibit up-regulated adhesion to the integrin ligands fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1). Here, we have examined T cell responses to purified antigenic class II complexes, alone or coimmobilized in the presence of FN or ICAM-1. T cell adhesion to immobilized peptide-MHC complexes alone stimulated suboptimal, but marked levels of IFN-gamma and IL-2 secretion, and this was accompanied by cell proliferation. T cell adhesion to both FN and ICAM-1 strongly augmented cytokine release and T cell proliferation. Activation of Vbeta3+ and Vbeta8+ T cell lines by isolated staphylococcal enterotoxin-MHC complexes was also examined, and surprisingly, a Vbeta8+ T cell line displayed significant cell adhesion or later response to staphylococcal enterotoxin B-MHC complexes only when Ag was coimmobilized with ICAM-1 or FN. The results demonstrate that adhesion of CD4+ T cells to ICAM-1 or FN activated by natural TCR ligands can strongly augment T cell signaling and downstream responses. Moreover, for some Ags, T cell interaction with accessory ligands may be critical in attaining a threshold level of receptor occupancy for cell activation.