Specificity of effector T lymphocytes in autologous graft-versus-host disease: role of the major histocompatibility complex class II invariant chain peptide.
Administration of the immunosuppressive drug cyclosporine after autologous bone marrow transplantation induces a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome termed autologous GVHD has significant antitumor activity. Associated with autologous GVHD is the development of T lymphocytes that recognize major histocompatibility complex (MHC) class II determinants, including self. The present studies attempted to characterize and define the molecular specificity of the effector T lymphocytes in autologous GVHD induced in patients with metastatic breast cancer. The results suggest that the effector cells associated with human autologous GVHD are CD8+ T lymphocytes expressing the alpha/beta T-cell receptor. Additional studies show that the effector T cells recognize MHC class II antigens in association with a peptide from the invariant chain (CLIP). Pretreatment of autologous lymphoblast target cells with anti-CLIP antibody completely blocked lysis mediated by autologous GVHD effector T cells. On the other hand, force loading this peptide markedly enhanced the susceptibility of the target cells to recognition by the autoreactive T cells. The recognition of the MHC class II CLIP complex may account for the novel specificity of the effector T cells associated with human autologous GVHD. Moreover, identification of the target peptide may allow for the development of novel immunotherapeutic strategies to enhance the antitumor efficacy of autologous GVHD.
Hess
A D
AD
Bone Marrow Transplantation Unit, Oncology Center, The Johns Hopkins University, Baltimore, MD 21287-8985, USA.
Bright
E C
EC
Thoburn
C
C
Vogelsang
G B
GB
Jones
R J
RJ
Kennedy
M J
MJ
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000502:physiology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D001943:Breast Neoplasms; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular; D007959:Lymphocyte Culture Test, Mixed; D008875:Middle Aged; D008969:Molecular Sequence Data; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014182:Transplantation, Autologous; D014407:Tumor Cells, Cultured
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C045084:invariant chain