TCR-ALPHA 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 c ellular immunology, several lines of evidence indicate that T-cell-rec eptor alpha-chain (TCR-alpha) is a critical component of suppressor fa ctors produced by these cells. Monoclonal non-specific suppressor fact or (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-lik e polypeptide and other subunit(s). Here we report that the 8000-MW ub iquitin homologue is associated with an intracellular TCR-alpha (but n ot TCR-beta) -like molecule and released from the cells. The affinity eluates obtained from the culture supernatants of E17 cells and concan avalin A (Con A)-activated splenocytes with anti-TCR-alpha monoclonal antibody (mAb) showed an antigen-non-specific, major histocompatibilit y complex (MHC)-non-restricted suppression. Immunoblot analysis demons trated that anti-TCR-alpha, but not anti-TCR-beta, mAb recognizes nati ve 70 000-MW MNSF. In addition, we found the dissociation of the 8000- MW polypeptide from the 62 000-MW TCR-alpha cross-reactive protein by hydrolase which cleaves isopeptide bonds. Thus the covalent attachment of ubiquitin-like protein(s) may be involved in the underlying mechan ism of suppressor T-cells and TCR-alpha-like molecule(s) might be a ma in link between antigen-specific and non-specific suppression.