The formation of a novel class Ib:gp180 complex on the surface of intestinal epithelial cells triggers a signaling cascade resulting in the activation of CD8+ suppressor T cells

Previous studies have shown that intestinal epithelial cells are capable of acting as APCs selectively activating CD8+ suppressor T cells. This activation appears to be mediated by a novel complex consisting of the class Ib molecule CDld and an associated epithelial cell surface glycoprotein, gplS0. We have postulated that this complex is recognized by the TCR:CD8 co-receptor complex on suppressor T cells and serves to induce their activation. Since gpl80 binds to any CD8 molecule, we wanted to determine whether IECs are targeting a selected subpopulation of "pre-suppressor" cells or whether the CDld:gpl80 complex was transducing a specific signal that promoted suppressor cell generation. To accomplish this, we dissected the signaling pathway activated following IEC:T cell co-cultures. Previous studies had shown that both CD8-associated p561ck and TCR-associated p59fyn were activated in these co-cultures. A two-fold experiment was performed: initially, the ability of IECs to activate both lck and fyn was studied in T cell:IEC co-cultures; then, the ability to recruit the protein tyrosine kinase ZAP70 and the proto-oncogenic substrate vav to both fyn and lck was investigated. Both CD8-associated Ick and TCR-associated fyn were activated by IECs. This activation resulted in the recruitment of zeta chain, ZAP70 and vav to fyn while lck associated with ZAP70 and vav. These experiments were then repeated in the presence or absence of an anti-CDld mAb, D5 or an antigpl80 mAb, B9. Activation of fyn but not lck was blocked by D5 while B9 inhibited IEC-induced activation of lck but not fyn. Furthermore, D5 inhibited the ability of ZAP70, zeta and vav to recruit to fyn but not to lck. Conversely, B9 appeared to inhibit the ability of both ZAP70 and vav to be recruited to lck but not fyn. Lastly, MAP kinase was activated in these co-cultures as well, suggesting that the signaling pathway was similar to that of CTLs. These data suggest that the activation of suppressor T ceils is not accomplished through a unique signaling cascade but rather through a similar cascade to cytolytic T cells. This suggests that T cells are committed at an earlier developmental stage to become either suppressor or cytolytic T cells.