Promiscuous recognition of major histocompatibility complex class II determinants in cyclosporine-induced syngeneic graft-versus-host disease: specificity of cytolytic effector T cells.
BACKGROUND
Administration of the immunosuppressive drug cyclosporine after syngeneic/autologous bone marrow transplantation paradoxically elicits a systemic autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome, termed autologous or syngeneic GVHD, is associated with the development of a highly restricted repertoire of cytolytic T lymphocytes that promiscuously recognizes major histocompatibility complex class II determinants, including self.


METHODS
Vbeta8.5+CD8+ effector lymphocytes and T-cell clones were isolated from Lewis rats with cylosporine-induced syngeneic GVHD. The specificity of the effector T cells and T-cell clones was examined in vitro. The pathogenicity of the T-cell clones was confirmed in vivo using a local graft-versus-host reaction assay.


RESULTS
Clonal analysis reveals that the pathogenic effector T cells recognize a peptide from the invariant chain termed CLIP in association with major histocompatibility complex class II determinants. Moreover, there appears to be an additional interaction between the N-terminal flanking region of CLIP and the Vbeta segment of the T cell receptor.


CONCLUSIONS
The results suggest that recognition of this highly conserved peptide along with the additional interaction between the flanking region and the T cell receptor may account for the promiscuous activity of the autologous/syngeneic GVHD autoreactive T cells.
Hess
A D
AD
Division of Hematologic Malignancies, Oncology Center, The Johns Hopkins University, Baltimore, Maryland 21287-8985, USA. adhess@welchlink.welch.jhu.edu
Thoburn
C
C
Horwitz
L
L
D000595:Amino Acid Sequence; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D016572:Cyclosporine; D003602:Cytotoxicity, Immunologic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008969:Molecular Sequence Data; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; C045084:invariant chain; D016572:Cyclosporine