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 journalArticlepeer-review

134 Scopus citations

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

ASJC Scopus subject areas

  • General

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