The low molecular mass polypeptides of secretory proteome of Mycobacterium tuberculosis are dominant targets for recognition by lymphocytes of human models of immunity to tuberculosis. In the present study, we evaluated the inherent immunogenicity of 102 individual polypeptides purified from low molecular mass region below 40kDa in mouse model of immunization. The aim of this study was to identify molecules relevant for development of subunit vaccine against tuberculosis based on high degree of immunogenecity. Here, we demonstrate that experimental multicomponent subunit vaccine (MSV) consisting of five immunodominant polypeptides with high immunogenicity (CFP-25, CFP-20.5, Ag85B, Ag85A and CPF-32) induced both cellular and humoral immune responses characterized by Th1 and Th2 cytokine induction and imparted significant protection when administered with DDA-MPL adjuvants in C57BL/6J mice. The degree of protection imparted by experimental MSV on the basis of decrease in CFU's from target organs (lungs and spleen) was comparable to BCG and total mycobacterial culture filtrate proteins (CFPs) based vaccines. These results, therefore, suggest the potential of multicomponent subunit vaccination against tuberculosis based on strongly immunogenic proteins of M. tuberculosis.