Mycobacterium tuberculosis Rv3615c is a highly immunodominant antigen and specifically induces potent Th1-type immune responses in tuberculosis pleurisy

T-cell responses have been demonstrated essential for preventing M .tb infection. The Th1-cytokines produced by T cells, such as INF-, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity. Here, we studied human pulmonary T-cell responses induced by M.tb -specific antigen Rv3615c, a protein with a similar size and sequence homology to ESAT-6 and CFP-10 which induced dominant CD4+ T-cell responses in human TB models. We characterized those T-cell responses including cytokine profiling, kinetic of activation, expansion, differentiation, TCR usage and signaling of activation induced by Rv3615c compared to other M.tb -specific antigens. The expanded CD4+ T cells induced by Rv3615c predominately produced Th1, however, less Th2 and Th17 cytokines and displayed effector/memory phenotypes (CD45RO+CD27-CD127-CCR7-). The magnitude of expansion and cytokine production was comparable to those induced by well-characterized ESAT-6, CFP-10 and BCG. Rv3615c contained multiple epitopes Rv3615c1-15, Rv3615c6-20, Rv3615c66-80, Rv3615c71-85 and Rv3615c76-90 that activated CD4+ T cells. The Rv3615c-specific CD4+ T cells shared biased of TCR Vβ 1, 2, 4, 5.1, 7.1...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research