T-CELL CLONES FROM A NON-LEPROSY EXPOSED SUBJECT RECOGNIZE THE MYCOBACTERIUM-LEPRAE 18-KD PROTEIN

Although Mycobacterium leprae shares many protein antigens with other mycobacterial species, there is a degree of specificity in the T cell response to the organism. This is evident in the failure of cross-prot ection between mycobacterial species and the specific unresponsiveness to M. leprae in lepromatous leprosy patients. The antigenic basis of this specificity is unresolved, but the M. leprae 18-kD protein is one candidate because of its restricted distribution and the isolation of M. leprae-specific T cell clones reactive with the protein from M. le prae-vaccinated subjects. In the course of analysing the human T cell repertoire to mycobacteria we have isolated further CD4(+) T cell clon es reactive with this protein from a subject who had never been expose d to ill. leprae. These clones did not respond to other mycobacteria, including M. tuberculosis and ill. bovis (BCG). In addition, they were unreactive with the M. tuberculosis 16-kD protein which has recently been shown to have limited amino acid identity with the M. leprae 18-k D protein. Both clones reacted with peptide 38-50 from the M. leprae 1 8-kD protein, the T cell response to which is restricted by HLA-DR4. A lthough homologues for the gene encoding the hi. leprae 18-kD antigen have been identified in M. avium and M. intracellulare, the clones fai led to respond to preparations of M, avium. Both clones secreted inter feron-gamma (IFN-gamma) and tumour necrosis factor-beta (TNF-beta) and were cytolytic against autologous targets pulsed with peptide 38-50 o r the 18-kD protein. The nature of the antigen which stimulates this a pparently 'M. leprae-specific' response is unknown. Nevertheless the r ecognition of the 18-kD protein by individuals not exposed to leprosy indicates that this protein may not be suitable as a reagent to distin guish between infection with hi. leprae and other pathogenic mycobacte ria.