TY - JOUR
T1 - Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis
AU - Cho, Sungae
AU - Mehra, Vijay
AU - Thoma-Uszynski, Sybille
AU - Stenger, Steffen
AU - Serbina, Natalya
AU - Mazzaccaro, Richard J.
AU - Flynn, Joanne L.
AU - Barnes, Peter F.
AU - Southwood, Scott
AU - Celis, Esteban
AU - Bloom, Barry R.
AU - Modlin, Robert L.
AU - Sette, Alessandro
PY - 2000/10/24
Y1 - 2000/10/24
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.210391497
DO - 10.1073/pnas.210391497
M3 - Article
C2 - 11035787
AN - SCOPUS:12944316446
SN - 0027-8424
VL - 97
SP - 12210
EP - 12215
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -