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

Content Provider	PubMed Central
Author	Cho, Sungae Mehra, Vijay Sybille, Thoma-uszynski 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
Copyright Year	2000
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 A0201-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-A0201 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.
Starting Page	12210
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	22
Volume Number	97
Language	English
Publisher	The National Academy of Sciences
Publisher Date	2000-10-24
Access Restriction	Open
Rights Holder	The National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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