Augmentation of mature CD4+ T cell responses to isolated antigenic class II proteins by fibronectin and intercellular adhesion molecule-1.
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.
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R. W. Johnson Pharmaceutical Research Institute, La Jolla, CA 92037, USA.
O'Rourke
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005353:Fibronectins / Q000502:physiology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D017469:Receptors, Fibronectin / Q000502:physiology; D018089:Superantigens / Q000502:physiology
D005353:Fibronectins; D000949:Histocompatibility Antigens Class II; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D017469:Receptors, Fibronectin; D018089:Superantigens; D018799:Intercellular Adhesion Molecule-1