International Immunology, Vol. 11, No. 3, 407-416,
March 1999
© 1999 Japanese Society for Immunology
Changes in the strength of co-stimulation through the B7/CD28 pathway alter functional T cell responses to altered peptide ligands
Center For Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
1 Department of Adult Oncology, Dana Farber Cancer Instiute and Harvard Medical School, Boston, MA 02115, USA
Correspondence to: V. K. Kuchroo
T cells require a TCR and a co-stimulatory signal for activation. We have examined the effect of the strength of TCR and co-stimulatory signals on proliferation and production of cytokines by differentiated T cell clones. The TCR signal was varied using antigen dose and altered peptide ligands. The co-stimulatory signal was varied by using as antigen-presenting cells, Chinese hamster ovary cell transfectants that express different levels of the B7-1 molecule with similar levels of MHC class II. Our results show that the level of co-stimulation has a profound effect on the response to an antigen, and that a strong co-stimulatory signal can convert a weak agonist into a full agonist and an agonist into a superagonist. Antigenicity is not absolute but a function of the strengths of the TCR and co-stimulatory signals. Increasing the strength of co-stimulation can lower antigen concentration required for maximal proliferative responses by T cell clones by 5 log. These results show that the level of expression of co-stimulatory molecules will profoundly regulate T cell clonal expansion and effector functions.
Keywords: altered peptide ligands, B7-1, CD80, co-stimulation, experimental autoimmune encephalomyelitis, Th1, Th2
Transmitting editor: L. Steinman
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