Comprehensive definition of human immunodominant CD8 antigens in tuberculosis

Deborah Lewinsohn, Gwendolyn M. Swarbrick, Byung Park, Meghan E. Cansler, Megan D. Null, Katelynne G. Toren, Joy Baseke, Sarah Zalwango, Harriet Mayanja-Kizza, Lashaunda L. Malone, Melissa Nyendak, Guanming Wu, Kristi Guinn, Shannon McWeeney, Motomi (Tomi) Mori, Keith A. Chervenak, David R. Sherman, W. Henry Boom, David Lewinsohn

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 tuberculosis-infected 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.

Original languageEnglish (US)
Article number8
Journalnpj Vaccines
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2017

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CD8 Antigens
Immunodominant Epitopes
Mycobacterium tuberculosis
Tuberculosis
Tuberculosis Vaccines
T-Lymphocytes
Proteins
Latent Tuberculosis
BCG Vaccine
Enzyme-Linked Immunospot Assay
Peptide Library
Vaccinia
CD4 Antigens
Validation Studies
Proteome
Cell Wall
Interferons
Vaccines
Alleles
Genome

ASJC Scopus subject areas

  • Pharmacology
  • Infectious Diseases
  • Immunology
  • Pharmacology (medical)

Cite this

Comprehensive definition of human immunodominant CD8 antigens in tuberculosis. / Lewinsohn, Deborah; Swarbrick, Gwendolyn M.; Park, Byung; Cansler, Meghan E.; Null, Megan D.; Toren, Katelynne G.; Baseke, Joy; Zalwango, Sarah; Mayanja-Kizza, Harriet; Malone, Lashaunda L.; Nyendak, Melissa; Wu, Guanming; Guinn, Kristi; McWeeney, Shannon; Mori, Motomi (Tomi); Chervenak, Keith A.; Sherman, David R.; Boom, W. Henry; Lewinsohn, David.

In: npj Vaccines, Vol. 2, No. 1, 8, 01.12.2017.

Research output: Contribution to journalArticle

Lewinsohn, D, Swarbrick, GM, Park, B, Cansler, ME, Null, MD, Toren, KG, Baseke, J, Zalwango, S, Mayanja-Kizza, H, Malone, LL, Nyendak, M, Wu, G, Guinn, K, McWeeney, S, Mori, MT, Chervenak, KA, Sherman, DR, Boom, WH & Lewinsohn, D 2017, 'Comprehensive definition of human immunodominant CD8 antigens in tuberculosis', npj Vaccines, vol. 2, no. 1, 8. https://doi.org/10.1038/s41541-017-0008-6
Lewinsohn, Deborah ; Swarbrick, Gwendolyn M. ; Park, Byung ; Cansler, Meghan E. ; Null, Megan D. ; Toren, Katelynne G. ; Baseke, Joy ; Zalwango, Sarah ; Mayanja-Kizza, Harriet ; Malone, Lashaunda L. ; Nyendak, Melissa ; Wu, Guanming ; Guinn, Kristi ; McWeeney, Shannon ; Mori, Motomi (Tomi) ; Chervenak, Keith A. ; Sherman, David R. ; Boom, W. Henry ; Lewinsohn, David. / Comprehensive definition of human immunodominant CD8 antigens in tuberculosis. In: npj Vaccines. 2017 ; Vol. 2, No. 1.
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