SPECIFICITY OF EFFECTOR T-LYMPHOCYTES IN AUTOLOGOUS GRAFT-VERSUS-HOSTDISEASE - ROLE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II INVARIANT CHAIN PEPTIDE
Ad. Hess et al., SPECIFICITY OF EFFECTOR T-LYMPHOCYTES IN AUTOLOGOUS GRAFT-VERSUS-HOSTDISEASE - ROLE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II INVARIANT CHAIN PEPTIDE, Blood, 89(6), 1997, pp. 2203-2209
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.