THE MYCOBACTERIAL SECRETED ANTIGEN-85 COMPLEX POSSESSES EPITOPES THATARE DIFFERENTIALLY EXPRESSED IN HUMAN LEPROSY LESIONS AND MYCOBACTERIUM-LEPRAE-INFECTED ARMADILLO TISSUES

The granulomatous skin lesions in leprosy are thought to be initiated by the immune response to certain antigens of the causative agent, Myc obacterium leprae. The antigen 85 complex is one of the major targets in the immune response to M. leprae infection. In the present study, a panel of previously characterized monoclonal antibodies (MAbs) (3A8, Rb2, A4g4, A2h11, Pe12, and A3c12) reacting with different epitopes of the 85 complex proteins of Mycobacterium tuberculosis and M. leprae w as employed in a comparative immunohistological analysis to demonstrat e the in situ expression of 85 complex antigenic epitopes in leprosy l esions across the clinical spectrum and in M. leprae-infected armadill o liver tissues. These MAbs showed a heterogeneous staining pattern in a given leprosy lesion. In highly bacilliferous borderline and leprom atous leprosy lesions, MAbs Rb2, A4g4, A2h11, and Pe12 stained clear r od-shaped M. leprae bacilli within macrophages, and the degree of stai ning correlated with the bacillary index of the lesion. On the other h and, MAbs 3A8 and A3cl2 staining was mostly seen as a diffuse staining pattern within interstatial spaces and on the membranes of the infilt rated cells but not the bacilli. In paucibacillary borderline and tube rculoid leprosy lesions, only 3A8, Rb2, and A3c12 showed distinct stai ning in association with infiltrates in the granuloma. None of these M Abs showed any detectable reaction with control nonleprosy skin lesion s, while MAb A3c12 positively stained the granulomas of both leprosy a nd control specimens. In situ reactivity of these MAbs with M. leprae- infected armadillo liver tissues also showed a heterogeneous staining pattern. Interestingly, a clear difference in expression of these epit opes was observed between armadillo tissues and human leprosy lesions. By immunogold ultracytochemistry, we further showed the differential localization of these MAb-reactive epitopes on the cell surface, in th e cytosol, and at the vicinity of M. leprae within Kufper cells of arm adillo liver tissues. Our results indicate that these antigenic epitop es of the antigen 85 complex are differentially expressed in leprosy l esions and infected armadillo tissues and that they could be target de terminants in the immunopathological responses during M. leprae infect ion.