THE HSP90-SPECIFIC INHIBITOR, GELDANAMYCIN, BLOCKS CD28-MEDIATED ACTIVATION OF HUMAN T-LYMPHOCYTES

The 90 kDa heat shock protein (Hsp90) is a molecular chaperone aiding the folding of nuclear hormone receptors and protein kinases. Hsp90-me diated folding can be disrupted by the Hsp90-specific drug, geldanamyc in. Here we provide evidence for the inhibition of the CD28-specific B W 828 antibody-mediated activation of human T lymphocyte proliferation , IL-2 secretion and IL-2 receptor expression by geldanamycin. Our res ults suggest that the major cytoplasmic chaperone, Hsp90, plays an imp ortant role in CD28-mediated T lymphocyte activation.