Longitudinal analysis of Mycobacterium tuberculosis 19-kDa antigen-specific T cells in patients with pulmonary tuberculosis: Association with disease activity and cross-reactivity to a peptide from HIVenv gp120

Abstract

CD8+ T cells play a central role in immune protection against infection with Mycobacterium tuberculosis. One of the target epitopes for anti-M. tuberculosis directed CD8+ T cells is the HLA-A2-restricted 19-kDa lipoprotein pepticle VLTDGNPPEV. T cell clones directed against this epitope recognized not only the nominal peptide ligand, but also a closely related peptide (VPTDPNPPE) from the HIV envelope gp120 (HIVenv gp120) protein characterized by IFN-γ release. This cross-reactivity was confirmed in ex vivo in M. tuberculosis 19-kDa tetramer-sorted T cells from patients with tuberculosis and in HIVgp120 tetramer- reactive T cells sorted from HIV+ patients. M. tuberculosis 19-kDa antigen-reactive T cells were present in HLA-A2+ patients (10/10) with HIV infection with no evidence of M. tuberculosis infection, but they are absent in peripheral blood lymphocytes from healthy HLA-A2+ individuals (10/10). M. tuberculosis 19-kDa antigen-reactive T cells were elevated in acute pulmonary tuberculosis, declined with response to therapy (7/10 patients) and resided in the terminally differentiated CD8+ T cell subset. CD8+ cross-reactive T cells recognizing HIVenv or M. tuberculosis 19-kDa antigens may contribute to pathogenesis in individuals co-infected with both pathogens and may also present a marker for active tuberculosis.