HYBRID ANTIBODY-MEDIATED VETO OF CYTOTOXIC T-LYMPHOCYTE RESPONSES

Strategies are being sought that allow the induction of specific toler ance to allogeneic transplants without affecting other immune function s. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymph ocyte precursors to antigens expressed by those CD8(+) veto cells. Yet , veto inhibition will not be able to provide complete tolerance to al logeneic gaits since it only operates on cell populations that express CD8. Other types of cells prevalent in most organs express different tissue-specific antigens that are recognized by alloreactive T-cells. Therefore, complete tolerance to an allogeneic transplant can only be achieved if all cellular components within the graft acquire the immun e-inhibitory function. Here, we studied whether the veto effect could be exploited for this purpose nevertheless. We produced a hybrid antib ody (HAb) combining a mAb specific for a class I MHC molecule with a s oluble CD8 molecule. We found that this HAb specifically and effective ly transferred veto inhibition to different stimulator cell population s. Thus, we have developed a strategy that promises to selectively and completely tolerize graft-specific CTLs without affecting normal immu ne responses.