A peptidoglycan protein complex purified from M Leprae cell walls contains most or all immunodominat M leprae T-cell antigens

The outcome of an infection with Mycobacterium leprae is correlated with the T-cell-mediated immune response developed against this pathogenic agent. The identification of M. leprae antigens that are recognized by T cells is therefore of great importance. In this paper we present the results of in vitro lymphoproliferation assays in which T-cell reactivity was measured against a peptidoglycan-protein complex (PPC) which was purified from the cell wall of M. leprae. Twelve M. leprae-reactive T-cell clones with different antigen specificities from a tuberculoid (TT) leprosy patient showed proliferative responses, but only when PPC was presented by HLA-DR-matched antigen-presenting cells (APCs). Four of these clones were known to react with the recombinant mycobacterial 65-kDa protein. A tetanus-toxoid-reactive T-cell line from a healthy control was not stimulated by this complex, supporting the idea that the stimulation by PPC was antigen specific. Both PPD-reactive and M. leprae-reactive T-cell lines from healthy individuals were stimulated by PPC. However, when this complex was presented to PPD-reactive T-cell lines derived from two lepromatous (LL) leprosy patients, we did not observe any proliferative responses. From these results we conclude that PPC contains most or all of the antigens which stimulate M. leprae-reactive T cells in association with relevant HLA class II molecules, including the 65-kDa protein or at least some immunogenic parts of it