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Poly(Glu60Ala30Tyr10) (GAT)-induced IgG monoclonal antibodies cross-react with various self and non-self antigens through the complementarity determining regions. Comparison with IgM monoclonal polyreactive natural antibodies

Abstract : Previous studies have shown that the antibodies of the preimmune repertoire are able to bind to various auto- and xenoantigens including chemical haptens. Sequence analysis of two such murine monoclonal IgM natural autoantibodies showed that they are encoded by unmutated germ-line variable regions of the light and heavy chain (V alpha and VH) genes which were also found in various murine immune responses, like phenyl-oxazolone, dinitrophenyl, arsonate, phosphorylcholine and influenza virus hemagglutinin. These data raised the question as to whether induced antibodies possessing germ-line sequence are also able to react with autoantigens. To study this problem, anti-poly(Glu60Ala30Tyr10) (GAT) and anti-alprenolol (Alp) monoclonal antibodies, carrying similar VH and V alpha genes and the same IgG1 isotype, were examined for their capacity to react with several self and non-self antigens. The results showed that: (a) the anti-GAT antibodies tested reacted with different autoantigens, such as murine tubulin, actin and myosin as well as trinitrophenyl (TNP) and bovine serum albumin. Similarly, one of the anti-Alp showed weak reactivities for myosin, DNA, actin and TNP; (b) in contrast two other anti-Alp antibodies did not react with any of the tested antigens. Since the major differences between the oligoreactive anti-GAT and the monoreactive anti-Alp antibodies are in the complementarity determining regions (CDR) our results suggest that the observed cross-reactions are mediated by hypervariable loops. Sequence comparison of these antibodies indicate a possible correlation between cross-reactivity and the presence of aromatic and charged amino acids in the CDR.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03136467
Contributor : Marie de Tarragon <>
Submitted on : Tuesday, February 9, 2021 - 5:08:38 PM
Last modification on : Tuesday, March 2, 2021 - 3:16:59 AM

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Rosana González-Quintial, Roberto Baccalá, Pedro Maria Alzari, Clara Nahmias, Gilbert Mazza, et al.. Poly(Glu60Ala30Tyr10) (GAT)-induced IgG monoclonal antibodies cross-react with various self and non-self antigens through the complementarity determining regions. Comparison with IgM monoclonal polyreactive natural antibodies. European Journal of Immunology, Wiley-VCH Verlag, 1990, 20 (11), pp.2383-2387. ⟨10.1002/eji.1830201104⟩. ⟨pasteur-03136467⟩

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