4.5 Article

A novel molecular analysis of genes encoding catalytic antibodies

Journal

MOLECULAR IMMUNOLOGY
Volume 50, Issue 3, Pages 160-168

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2012.01.004

Keywords

Catalytic antibodies; Abzymes; Autoimmune diseases; Somatic hypermutations; Germlines

Funding

  1. Centre National de la Recherche Scientifique
  2. Institut National de la Sante et de la Recherche Medicale
  3. Universite Pierre et Marie Curie
  4. European Union
  5. Conseil Regional de Picardie
  6. Indo-French Center for Promotion of Advanced Research [4103-2]
  7. Agence Nationale de la Recherche [ANR-09-GENO-028]
  8. Japan Sciences and Technology Agency (Tokyo, Japan)

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Among the numerous questions remaining opened about catalytic antibodies (abzymes), the understanding of the origin of the genes encoding them is of vital significance. An original statistical analysis of genes encoding abzymes is described in the present report. Results suggested that these genes display a high conservation degree with their germline counterpart and a limited number of amino acid changes. Hence, on the contrary with high-affinity antibodies, maturation process by accumulation of somatic hypermutations is not required for the catalytic function. We demonstrated that despite a weak somatic mutation rate, the physicochemical properties of mutated amino acid (AA) are predominantly dissimilar with that of the germline AA. Further, we developed a novel approach in order to analyze the nature of genes encoding catalytic antibodies. For the first time, an unexpected and significant high level expression of rare gene subgroups was noticed and emphasized. The data described in this paper would lay the foundation for future studies about origin of genes encoding catalytic antibodies. (c) 2012 Elsevier Ltd. All rights reserved.

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