title: Mycobacterial Cpn10 promotes recognition of the mammalian homologue by a mycobacterium-specific antiserum.
abstract: Self-tolerance, a key feature of the immune system, is still a matter of intense debate. We give here evidence for a peculiar behavior of an antiserum against Mycobacterium tuberculosis chaperonin 10 (m-Cpn10), which could have implications for the mechanism of self-recognition by antibodies against non-self. We show that this antiserum can interact in terms of both inhibition of biological activity and physical association (immunoprecipitation), with the mammalian homologue of m-Cpn10, but only if the bacterial protein is present. Several lines of evidence led us to exclude that the two proteins physically associate to form heterocomplexes: (1) the behavior of the antiserum was not shared by a monoclonal antibody against m-Cpn10; (2) a matrix selective for human Cpn10 (h-Cpn10) did not co-purify m-Cpn10; (3) the distribution pattern in non-denaturing isoelectric focusing of labeled m-Cpn10 was not altered by the presence of the unlabeled h-Cpn10. We conclude therefore that the antiserum against M. tuberculosis Cpn10 also recognizes mammalian Cpn10, with an affinity/avidity regulated by the mycobacterial protein, or by the promotion of hetero-oligomerization. This emergence of self-recognition in the presence of M. tuberculosis Cpn10 could imply a breaking of self-tolerance in situations of infection or vaccination.
authors.affiliation: Istituto di Ricerche Farmacologiche 'Mario Negri', Via Eritrea 62, I-20157 Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Minto
authors.forename: G
authors.initials: G
authors.lastname: Galli
authors.forename: E
authors.initials: E
authors.lastname: Gianazza
authors.forename: I
authors.initials: I
authors.lastname: Eberini
authors.forename: G
authors.initials: G
authors.lastname: Legname
authors.forename: G
authors.initials: G
authors.lastname: Fossati
authors.forename: D
authors.initials: D
authors.lastname: Modena
authors.forename: F
authors.initials: F
authors.lastname: Marcucci
authors.forename: P
authors.initials: P
authors.lastname: Mascagni
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
authors.forename: M
authors.initials: M
authors.lastname: Fratelli
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000918:Antibody Specificity; D015551:Autoimmunity; D018835:Chaperonin 10 / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011485:Protein Binding; D017634:Self Tolerance; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D000907:Antibodies, Bacterial; D018835:Chaperonin 10