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 pepti de 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 (DRB11501) and human B7-1 or B7-2 as APC, presentation of native myelin basic protein (MBP) p85-99 pepti de Ag or a partial agonist of MBP p85-99 induced equivalent T cell act ivation as measured by [H-3]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 r esulted in significant T cell activation as measured by [H-3]TdR incor poration and cytokine secretion. These data suggest that decreasing th e strength of the signal provided to the TCR allows differences in B7- 1 and B7-2 signaling to be observed. Thus, the costimulatory environme nt during T cell activation may tie a mechanism of regulating T cell c ross-reactivity; in the periphery.