MYCOBACTERIAL CPN10 PROMOTES RECOGNITION OF THE MAMMALIAN HOMOLOG 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 b y antibodies against non-self. We show that this antiserum can interac t in terms of both inhibition of biological activity and physical asso ciation (immunoprecipitation), with the mammalian homologue of m-Cpn 1 0, but only if the bacterial protein is present. Several lines of evid ence led us to exclude that the two proteins physically associate to f orm heterocomplexes: (1) the behavior of the antiserum was not shared by a monoclonal antibody against m-Cpn10; (2) a matrix selective for h uman Cpn10 (h-Cpn10) did not co-purify m-Cpn10; (3) the distribution p attern in non-denaturing isoelectric focusing of labeled m-Cpn10 was n ot altered by the presence of the unlabeled h-Cpn10, We conclude there fore that the antiserum against M. tuberculosis Cpn10 also recognizes mammalian Cpn10, with an affinity/avidity regulated by the mycobacteri al protein, or by the promotion of hetero-oligomerization. This emerge nce of self-recognition in the presence of M. tuberculosis Cpn10 could imply a breaking of self-tolerance in situations of infection or vacc ination. (C) 1998 Elsevier Science B.V.