GLUCOSIDASE TRIMMING INHIBITORS PREFERENTIALLY PERTURB T-CELL ACTIVATION-INDUCED BY CD2 MAB

Glycosidase trimming inhibitors may be used to study contribution of N -linked glycan moieties in T cell function. We have studied the effect s of castanospermine (Cas), swainsonine(Swain), 1-deoxynojirimycin (dN M), and 1-deoxymannojirimycin (dMM) on T cell activation and different iation. Our analysis included a new dNM derivative, N-pentyl-1-deoxyno jirimycin (pentyldNM). Previous reports showed inhibitory action of tr imming inhibitors, such as Swain and Cas, on pokeweed mitogen-driven i mmunoglobulin (Ig) production. We extend these findings for pentyldNM and observed that glucosidase inhibitors, Cas and pentyldNM were effec tive in inhibiting CD2 and CD3 monoclonal antibody (mAb) driven Ig pro duction. The pattern of inhibition by mannosidase and glucosidase inhi bitors correlated with inhibitory action on T cell activation: only gl ucosidase trimming inhibitors (Cas and pentyldNM with comparable poten cy) perturbed mAb-induced T cell activation, in particular if induced by CD2 mAb. Expression of the early activation marker CD69 was not dec reased in the presence of these inhibitors, while addition of exogenou s recombinant interleukin-2 partially overcame inhibitory effects duri ng proliferation. These findings suggest that glucosidase, but not man nosidase, trimming inhibitors interfere with a late phase of T cell ac tivation. In addition, the enhanced sensitivity of CD2 mAb-induced pro liferation for glucosidase trimming inhibitors suggests dependence on N-linked glycans during CD2-mediated adhesion and triggering functions .