TCR‐α chain‐like molecule is involved in the mechanism of antigen‐non‐specific suppression of a ubiquitin‐like protein

Although existence of suppressor T cells is a controversial issue in cellular immunology, several lines of evidence indicate that T-cell-receptor α-chain (TCR-α) is a critical component of suppressor factors produced by these cells. Monoclonal non-specific suppressor factor (MNSF), a lymphokine produced by murine T-cell hybridoma, possesses pleiotrophic antigen-non-specific suppressive functions. Recently, we have shown that the 70 000-MW MNSF comprises an 8000-MW ubiquitin-like polypeptide and other subunit(s). Here we report that the 8000-MW ubiquitin homologue is associated with an intracellular TCR-α (but not TCR-β) -like molecule and released from the cells. The affinity eluates obtained from the culture supernatants of E17 cells and concanavalin A (Con A)-activated splenocytes with anti-TCR-α monoclonal antibody (mAb) showed an antigen-non-specific, major histocompatibility complex (MHC)-non-restricted suppression. Immunoblot analysis demonstrated that anti-TCR-α, but not anti-TCR-β, mAb recognizes native 70 000-MW MNSF. In addition, we found the dissociation of the 8000-MW polypeptide from the 62 000-MW TCR-α cross-reactive protein by hydrolase which cleaves isopeptide bonds. Thus the covalent attachment of ubiquitin-like protein(s) may be involved in the underlying mechanism of suppressor T-cells and TCR-α-like molecule(s) might be a main link between antigen-specific and non-specific suppression. hNSF, human non-specific suppressor factor MNSF, monoclonal non-specific suppressor factor Ubi-L, ubiquitin-like moiety.