Comprehensive definition of human immunodominant CD8 antigens in tuberculosis
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Date
2017
Journal Title
Journal ISSN
Volume Title
Publisher
NPJ vaccines
Abstract
Despite widespread use of the Bacillus Calmette-Guerin vaccine, tuberculosis, caused by infection with Mycobacterium tuberculosis,
remains a leading cause of morbidity and mortality worldwide. As CD8+ T cells are critical to tuberculosis host defense and a phase
2b vaccine trial of modified vaccinia Ankara expressing Ag85a that failed to demonstrate efficacy, also failed to induce a CD8+ T cell
response, an effective tuberculosis vaccine may need to induce CD8+ T cells. However, little is known about CD8, as compared to
CD4, antigens in tuberculosis. Herein, we report the results of the first ever HLA allele independent genome-wide CD8 antigen
discovery program. Using CD8+ T cells derived from humans with latent tuberculosis infection or tuberculosis and an interferon-γ
ELISPOT assay, we screened a synthetic peptide library representing 10% of the Mycobacterium tuberculosis proteome, selected to
be enriched for Mycobacterium tuberculosis antigens. We defined a set of immunodominant CD8 antigens including part or all of 74
Mycobacterium tuberculosis proteins, only 16 of which are previously known CD8 antigens. Immunogenicity was associated with the
degree of expression of mRNA and protein. Immunodominant antigens were enriched in cell wall proteins with preferential
recognition of Esx protein family members, and within proteins comprising the Mycobacterium tuberculosis secretome. A validation
study of immunodominant antigens demonstrated that these antigens were strongly recognized in Mycobacterium tuberculosisinfected
individuals from a tuberculosis endemic region in Africa. The tuberculosis vaccine field will likely benefit from this greatly
increased known repertoire of CD8 immunodominant antigens and definition of properties of Mycobacterium tuberculosis proteins
important for CD8 antigenicity.
Description
Keywords
Human immunodominant CD8 antigens, Tuberculosis
Citation
Lewinsohn, D. A., Swarbrick, G. M., Park, B., Cansler, M. E., Null, M. D., Toren, K. G., ... & Lewinsohn, D. M. (2017). Comprehensive definition of human immunodominant CD8 antigens in tuberculosis. NPJ vaccines, 2(1), 1-11. doi:10.1038/s41541-017-0008-6