Mycobacterial Cpn10 promotes recognition of the mammalian homologue by a mycobacterium-specific antiserum.
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.
Minto
M
M
Istituto di Ricerche Farmacologiche 'Mario Negri', Via Eritrea 62, I-20157 Milan, Italy.
Galli
G
G
Gianazza
E
E
Eberini
I
I
Legname
G
G
Fossati
G
G
Modena
D
D
Marcucci
F
F
Mascagni
P
P
Ghezzi
P
P
Fratelli
M
M
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
D000907:Antibodies, Bacterial; D018835:Chaperonin 10