Identification of novel epitopes from Mycobacterium tuberculosis (43.32)

Abstract

Abstract Mycobacterium tuberculosis (MTB) is the one of the worldwide leading cause of death from infectious disease. The MTB genome encodes just under 4,000 different ORFs, yet epitopes recognized by human CD4+ T cells, the key cellular effector of MTB immunity, have been described for less than 2%. Our present study addresses the discovery and validation of MTB CD4+ T cell epitopes presented by HLA Class II molecules. We have identified hundreds of MTB-specific epitopes by the combined use of epitope predictions and high-throughput ex vivo ELISPOT assays using PBMC from human donors latently infected with MTB. Specificity was demonstrated by parallel testing of non-TB infected control donors. These epitopes allow us to identify previously unknown CD4+ TB antigens. We are in the process of further validating these epitopes by examining the T cell phenotype, pattern of cytokine secretion associated with epitope responses and projected population coverage as determined by quantitative binding assays, as well as investigating T cell responses as a function of clinical outcome. This study determines the breadth of MTB responses in humans and it will establish whether there is a correlation between the antigens recognized by CD4+ T cells and serological reactivity and CD8+ T cells, antigen expression in different MTB forms and other structural and biological features associated with the antigens. In addition, these epitopes can be used as tools to understand the human immunity to TB.