Immunodominance of low molecular weight secretory polypeptides of Mycobacterium tuberculosis to induce cytotoxic T-lymphocyte response

The cytotoxic T-lymphocyte (CTL) responses to culture filtrate antigens of Mycobacterium tuberculosis H37Rv (RvCFP) and purified protein derivative (PPD) were investigated in active pulmonary tuberculosis patients, healthy tuberculosis contacts and non-contacts. Healthy tuberculin skin test (Mantoux) positive tuberculosis contacts demonstrated strong CTL response against RvCFP and Mantoux reactivity was found to correlate with CTL response. The specificity of CTL response in healthy Mantoux positive contacts was further assessed using different molecular weight fractions of RvCFP. Peripheral blood mononuclear cells (PBMCs) derived CTLs recognized multiple antigenic targets and demonstrated predominant cytotoxicity against low molecular weight (below 15 kDa) protein fractions as well as those migrated in the region of 30 kDa. Subsequently, evaluation of CTL responses against selected purified prominent T-cell antigens indicated maximum CTL response directed against Ag85 complex proteins; most notably Ag85A. From this study, it is suggested that identification of more mycobacterial antigens activating various CTL subsets could be an important step for the rational designing of future antituberculous vaccine.