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Inosine and N1-methylinosine within a synthetic oligomer mimicking the anticodon loop of human tRNAAla are major epitopes for anti-PL-12 myositis autoantibodies

  • H.F. BECKER (a1) (a2) (a3), Y. CORDA (a1) (a4), M.B. MATHEWS (a5), J.-L. FOURREY (a2) and H. GROSJEAN (a1)...

Abstract

Sera of some patients afflicted with the inflammatory disease myositis contain antibodies of the anti-PL-12 type. A fraction of these polyclonal autoantibodies specifically precipitates the fully matured human tRNAAla bearing the anticodon IGC (PL-12 antigen). Earlier work (Bunn & Mathews, 1987, Science 238:116–119) had shown that the epitopes are located entirely within the anticodon stem-loop of the tRNAAla. Here we demonstrate that human anti-tRNAAla autoantibodies immunoprecipitate a synthetic polyribonucleotide containing inosine (I) and N1-methylinosine (m1I) separated by 2 nt as in the anticodon stem-loop of human tRNAAla. The shortest polyribonucleotide that can be immunoprecipitated corresponds to the pentanucleotide IpGpCpm1IpUp, which corresponds to part of the anticodon loop of human tRNAAla and lacks the stem-loop structure. The efficiency of immunoprecipitation was about four times greater with longer polyribonucleotides capable of forming a stem-loop structure, and was abolished by altering the relative positions of I and m1I within the synthetic polynucleotide. Synthetic oligodeoxyribonucleotide analogs of the tRNAAla stem-loop, containing the sequence dIpdGdCdm1Ip, are not antigenic. Our results show that human anti-tRNAAla autoantibodies selectively recognize chemical details of modified nucleotides (the 6-keto group of inosine-34 and the 6-keto group and the N1-methyl groups of N1-methylinosine-37) within an anticodon loop structure of a tRNA molecule. We also describe the chemical synthesis of the phosphoramidite derivatives corresponding to N1-methylinosine and N1-methyl-2′-deoxyinosine for use in the automatic chemical synthesis of oligonucleotides containing N1-methylinosine and N1-methyl-2′-deoxyinosine.

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Corresponding author

Reprint requests to: Henri Grosjean, CNRS, Laboratoire d'Enzymologie et de Biochimie Structurales, 1, avenue de la Terrasse, Bat. 34, F-91198, Gif-sur-Yvette, France; e-mail: Henri.Grosjean@lebs.cnrs-gif.fr.

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The results of this paper were first reported at the Third Dresden Symposium on Autoantibodies held in Dresden on September 26\N28, 1996.

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Inosine and N1-methylinosine within a synthetic oligomer mimicking the anticodon loop of human tRNAAla are major epitopes for anti-PL-12 myositis autoantibodies

  • H.F. BECKER (a1) (a2) (a3), Y. CORDA (a1) (a4), M.B. MATHEWS (a5), J.-L. FOURREY (a2) and H. GROSJEAN (a1)...

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