title: 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.
authors: Unité d'Immunocytochimie, Institut Pasteur, Paris.
authors: R
authors: R
authors: González-Quintial
authors: R
authors: R
authors: Baccalà
authors: P M
authors: PM
authors: Alzari
authors: C
authors: C
authors: Nahmias
authors: G
authors: G
authors: Mazza
authors: M
authors: M
authors: Fougereau
authors: S
authors: S
authors: Avrameas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001665:Binding Sites; D003429:Cross Reactions; D004247:DNA / Q000276:immunology; D005803:Genes, Immunoglobulin; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011108:Polymers
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010455:Peptides; D011108:Polymers; C020749:GAT; D004247:DNA