Oligodendrocyte-specific autoreactive T cells using an alpha/beta T-cell receptor kill their target without self...

The oligodendrocyte (Od), a glial cell that produces myelin in the central nervous system, may be a target for autoreactive T cells in autoimmune demyelinating processes, although not expressing major histocompatibility complex (MHC) products. To analyze Od-T-cell interactions, we selected from normal SJL/J mouse splenocytes sensitized in vitro by Lewis rat Od a T-cell clone, named C2, exhibiting a surface phenotype of mature T cell (Thy 1+, CD3+, CD8+, CD4-, asialo-GM1-). C2 T cells displayed a specific cytotoxicity to syngeneic Od as well as to rat Od, but not to astrocytes or lymphoblasts, or to YAC-1 cells, a target for natural killer and lymphokine-activated killer activity. The T-cell receptor of clone C2 was found to be a CD3-associated alpha/beta-chain heterodimer similar to that usually expressed by antigen-specific MHC-restricted mature T cells. Attempts to block the C2-mediated cytolysis by a series of monoclonal antibodies showed that both the CD3-T-cell receptor complex and the CD8 accessory molecule were required for OD-T-cell interaction and confirmed the lack of involvement of polymorphic MHC products as epitope-presenting structures. Antibodies directed against a surface Od glycoprotein, previously shown to elicit demyelinating autoantibodies in experimental autoimmune encephalomyelitis, fully blocked the cytotoxicity of T-cell clone C2 to its Od target. These data suggest that an epitope of a surface Od glycoprotein may be directly and specifically recognized and killed by autoreactive T cells expressing an alpha/beta receptor without conventional MHC restriction.