INTERFERON INDUCTION OF HUMAN TRYPTOPHANYL-TRANSFER-RNA SYNTHETASE SAFEGUARDS THE SYNTHESIS OF TRYPTOPHAN-RICH IMMUNE-SYSTEM PROTEINS - A HYPOTHESIS

Ever since the discovery that the human tryptophanyl-tRNA synthetase ( TrpRS)-encoding gene is induced by interferon (IFN) [J. Fleckner et al ., Proc. Natl. Acad. Sci. USA 88 (1991) 11520-11524] and contains IFN- response regulatory elements [Frolova et al., Gene 128 (1993) 237-245] , the biological rationale for this induction has remained unresolved. A survey of immune system proteins in this study reveals that the hum an major histocompatibility complex (MHC) antigens, beta-2-microglobul in (beta MG) and complement factor B, which are known to be induced by IFN, together with immunoglobulins (Ig) are all exceptionally enriche d in Trp residues, as compared to human proteins in general. It also r eveals the conservation of a sequence motif, CX(10-17)WX(26-62)C, in I g domains. The conservation of this sequence motif and the utility of Trp residues within antigen-binding sites clearly contribute to the Tr p enrichment in Ig. These observations suggest a biological rationale for the induction of TrpRS by IFN in safeguarding Trp incorporation fo r the IFN-enhanced synthesis of immunological molecules.