Weak peptide agonists reveal functional differences in B7-1 and B7-2 costimulation of human T cell clones.
The influence of costimulation on the T cell response to altered peptide ligands that act as either partial or weak agonists for human CD4+ T cell clones was examined. Using stable Chinese hamster ovary (CHO) cell transfectants expressing DR2 (DRB1*1501) and human B7-1 or B7-2 as APC, presentation of native myelin basic protein (MBP) p85-99 peptide Ag or a partial agonist of MBP p85-99 induced equivalent T cell activation as measured by [3H]TdR incorporation and cytokine secretion. In marked contrast, presentation of cross-reactive peptides of MBP p85-99 that act as weak agonists with B7-1, but not B7-2, costimulation resulted in significant T cell activation as measured by [3H]TdR incorporation and cytokine secretion. These data suggest that decreasing the strength of the signal provided to the TCR allows differences in B7-1 and B7-2 signaling to be observed. Thus, the costimulatory environment during T cell activation may be a mechanism of regulating T cell cross-reactivity in the periphery.
Anderson
D E
DE
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Ausubel
L J
LJ
Krieger
J
J
Höllsberg
P
P
Freeman
G J
GJ
Hafler
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001327:Autoimmune Diseases / Q000209:etiology; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D016466:CHO Cells; D002999:Clone Cells; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D010446:Peptide Fragments