Human T-cell clones recognize a major M. leprae protein antigen expressed in E. coli

Abstract

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. As with other intracellular parasites, protective immunity is dependent on T cells and cell-mediated immunity. In animal models, immunization with killed armadillo-derived M. leprae elicits strong T-cell responses, delayed-type hypersensitivity and protection against viable challenge. We have recently shown that killed M. leprae can induce delayed-type hypersensitivity in healthy human volunteers. Identification of the M. leprae antigens that are recognized by T cells and may be involved in protection has been hampered by the inability to cultivate the organism in vitro and by difficulties in antigen purification from limited quantities of armadillo-derived bacillus. Because genes for the major protein antigens of M. leprae as seen by mouse monoclonal antibodies have been isolated, it has become possible to test whether these individual antigens are recognized by T cells. We screened crude lambda gtll phage lysates of Escherichia coli containing individual M. leprae antigens using M. leprae-specific T-cell clones isolated from M. leprae-vaccinated volunteers. Using this method, we find that nearly half of the M. leprae-specific T-cell clones are stimulated to proliferate by lysates containing an epitope of a M. leprae protein of relative molecular mass 18,000 (18K).

The identification of T cell epitopes inMycobacterium tuberculosisusing human T lymphocyte clones

“…Clones P48 and P57 demonstrated a different pattern of specificity in that they proliferated predominantly to M. tuberculosis and M. bovis, with reduced reactivity to M. kansasii (Table 1). Specificity analysis of H37Rv induced T cell clones isolated from a BCG vaccinated individual (16,17) support these findings that the major component of the T cell response to M. tuberculosis is cross reactive with that directed against M. bovis. Similar ly cross reactive T cell clones from leprosy patients have been identified (18,19).…”

“…Similar ly cross reactive T cell clones from leprosy patients have been identified (18,19). However as regards the recognition of M. leprae derived antigens a much greater proportion of the T cell response is against species-specific epitopes as determined at the clonal level (17,18). It is of interest to note that the diversity of the murine B cell repertoire to M. tuberculosis is more cross reace as compared to that directed against M. leprae (4-6) .…”

A Novel Mycobacterial Antigen Relevant to Cellular Immunity Belongs to a Family of Secreted Lipoproteins

“…Since protective immunity against Mycobacterium tuberculosis is mediated by the cellular immune system [2], a subunit vaccine approach has to rely on application of key antigens recognized by T cells with protective effector functions within an HLA heterogenous population. In this context a large number of biochemically purified and recombinantly expressed cytosolic as well as secreted mycobacterial antigens have been identified and characterized with respect to primary structure, T cell epitopes, and HLA restriction [3][4][5][6][7][8][9][10][11][12]. Recent results, mainly from the mouse system, suggest that the secreted antigens, due to their early and efficient presentation to the immune system, have the capacity to serve as protective antigens and hence represent relevant subunit vaccine candidates [13][14][15][16].…”

Lack of cytotoxic activity against Mycobacterium leprae 65-kD heat shock protein (hsp) in multibacillary leprosy patients

“…leprae have been characterized [1 4], and they have been recognized by Myco. leprae-reactive T cell clones [5][6][7] and sera from leprosy patients [8 10]. Proliferative responses of T cells from healthy Myco.…”