SPECIFICITY OF EFFECTOR T-LYMPHOCYTES IN AUTOLOGOUS GRAFT-VERSUS-HOSTDISEASE - ROLE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II INVARIANT CHAIN PEPTIDE

Administration of the immunosuppressive drug cyclosporine after autolo gous bone marrow transplantation induces a systemic autoimmune syndrom e resembling graft-versus-host disease (GVHD). This syndrome termed au tologous GVHD has significant antitumor activity. Associated with auto logous GVHD is the development of T lymphocytes that recognize major h istocompatibility complex (MHC) class II determinants, including self. The present studies attempted to characterize and define the molecula r specificity of the effector T lymphocytes in autologous GVHD induced in patients with metastatic breast cancer. The results suggest that t he effector cells associated with human autologous GVHD are CD8(+) T l ymphocytes expressing the alpha/beta T-cell receptor, Additional studi es show that the effector T cells recognize MHC class II antigens in a ssociation with a peptide from the invariant chain (CLIP). Pretreatmen t of autologous lymphoblast target cells with anti-CLIP antibody compl etely blocked lysis mediated by autologous GVHD effector T cells, On t he other hand, force loading this peptide markedly enhanced the suscep tibility of the target cells to recognition by the autoreactive T cell s. The recognition of the MHC class II CLIP complex may account for th e novel specificity of the effector T cells associated with human auto logous GVHD, Moreover, identification of the target peptide may allow for the development of novel immunotherapeutic strategies to enhance t he antitumor efficacy of autologous GVHD. (C) 1997 by The American Soc iety of Hematology.