Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis

Sungae Cho, Vijay Mehra, Sybille Thoma-Uszynski, Steffen Stenger, Natalya Serbina, Richard J. Mazzaccaro, Joanne L. Flynn, Peter F. Barnes, Scott Southwood, Esteban Celis, Barry R. Bloom, Robert L. Modlin, Alessandro Sette

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Studies of mouse models of tuberculosis (TB) infection have indicated a central role for MHC class I-restricted CD8+ T cells in protective immunity. To define antigens and epitopes of Mycobacterium tuberculosis (MTB) proteins that are presented by infected cells to CD8+ T cells, we screened 40 MTB proteins for HLA class I A*0201-binding motifs. Peptides that bound with high affinity to purified HLA molecules were subsequently analyzed for recognition by CD8+ cytotoxic T lymphocytes. We identified three epitopes recognized by CD8+ T cells from patients recovering from TB infection. Those three epitopes were derived from three different antigens: thymidylate synthase (ThyA30-38), RNA polymerase β-subunit (RpoB127-135), and a putative phosphate transport system permease protein A-1 (PstA175-83). In addition, CD8+ T cell lines specific for three peptides (ThyA30-38, PstA175-83, and 85B15-23) were generated from peripheral blood mononuclear cells of normal HLA-A*0201 donors. These CD8+ T cell lines specifically recognized MTB-infected macrophages, as demonstrated by production of IFN-γ and lysis of the infected target cells. Finally, CD8+ cytotoxic T lymphocytes reduced the viability of the intracellular MTB, providing evidence that CD8+ T cell recognition of MHC class I-restricted epitopes of these MTB antigens can contribute to effective immunity against the pathogen.

Original languageEnglish (US)
Pages (from-to)12210-12215
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number22
DOIs
StatePublished - Oct 24 2000

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Tuberculosis
T-Lymphocytes
Epitopes
Mycobacterium tuberculosis
Cytotoxic T-Lymphocytes
Immunity
Cell Line
Thymidylate Synthase
Peptides
Membrane Transport Proteins
Staphylococcal Protein A
DNA-Directed RNA Polymerases
Infection
Blood Cells
Proteins
Macrophages
Phosphates
Tissue Donors
Antigens
Mycobacterium tuberculosis antigens

ASJC Scopus subject areas

  • General

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Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis. / Cho, Sungae; Mehra, Vijay; Thoma-Uszynski, Sybille; Stenger, Steffen; Serbina, Natalya; Mazzaccaro, Richard J.; Flynn, Joanne L.; Barnes, Peter F.; Southwood, Scott; Celis, Esteban; Bloom, Barry R.; Modlin, Robert L.; Sette, Alessandro.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 22, 24.10.2000, p. 12210-12215.

Research output: Contribution to journalArticle

Cho, S, Mehra, V, Thoma-Uszynski, S, Stenger, S, Serbina, N, Mazzaccaro, RJ, Flynn, JL, Barnes, PF, Southwood, S, Celis, E, Bloom, BR, Modlin, RL & Sette, A 2000, 'Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 22, pp. 12210-12215. https://doi.org/10.1073/pnas.210391497
Cho, Sungae ; Mehra, Vijay ; Thoma-Uszynski, Sybille ; Stenger, Steffen ; Serbina, Natalya ; Mazzaccaro, Richard J. ; Flynn, Joanne L. ; Barnes, Peter F. ; Southwood, Scott ; Celis, Esteban ; Bloom, Barry R. ; Modlin, Robert L. ; Sette, Alessandro. / Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 22. pp. 12210-12215.
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