Putative N-terminal sequence of murine soluble immune response suppressor (SIRS): significant homology with short neurotoxin 1

Soluble immune response suppressor (SIRS) is a low-molecular-weight protein (˜10,000 daltons) produced by mitogen- or interferon-activated T lymphocytes that can block development of humoral or cell-mediated immune responses in vivo or in vitro. As previously reported, murine SIRS is heterogeneous, eluting in two broad peaks on high performance reverse phase chromatography as well as displaying several broad isoelectric point forms. A putative N-terminal 21 amino acid sequence has been obtained for one of the less hydrophobic isoforms, SIRS-α7. The sequence of SIRS-α7 is unique in mammals but shows a remarkable homology to the family of short neurotoxins (short neurotoxin I) found in sea snake, adder, and cobra species. A degenerate oligonucleotide probe based on the protein sequence was synthesized and was shown to hybridize to SIRS messenger RNA as measured by SIRS synthesis in a rabbit reticulocyte lysate system. A synthetic polypeptide based on the 21-residue sequence was also prepared and coupled to thyroglobulin or keyhole limpet hemocyanin. These were used to prepare rabbit antisera that neutralize SIRS bioactivity and precipitate authentic SIRS.