Promiscuous recognition of major histocompatibility complex class II determinants in cyclosporine-induced syngeneic graft-versus-host disease: Specificity of cytolytic effector T cells

Allan D. Hess, Christopher Thoburn, Louis Horwitz

Research output: Contribution to journalArticlepeer-review

Abstract

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. Vβ8.5+CD8+ effector lymphocytes and T-cell clones were isolated from Lewis rate 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 Vβ segment of the T cell receptor. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)785-792
Number of pages8
JournalTransplantation
Volume65
Issue number6
DOIs
StatePublished - Mar 27 1998

ASJC Scopus subject areas

  • Transplantation

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