HLA-B*35-restricted CD8 T cell epitopes in the antigen 85 complex of Mycobacterium tuberculosis.
Few target epitopes have been described for human CD8 T lymphocytes in antigens of Mycobacterium tuberculosis. By use of a reverse immunogenetics approach, 23 motif-bearing peptides of the Ag85 complex were tested for binding to HLA-B*35, one of the common B-types in West Africa. Three 9-mer peptides bound with high affinity to HLA-B*3501 and displayed low dissociation rates of peptide-major histocompatibility complexes (MHCs). IC(50) and half-life values of peptide-MHC class I complexes were in the same range as reported earlier for other immunogenic peptides. Immune responses against peptide Ag85C (aa 204-212) WPTLIGLAM were characterized in detail. Peptide-stimulated effector cells were able to kill macrophages infected with M. tuberculosis or bacille Calmette-Guérin. Peptide-specific CD8 T cells could be visualized by using HLA-B*3501 tetramers and were shown to produce interferon-gamma and tumor necrosis factor-alpha. Together with other published epitopes, these peptides can be used to study more closely the role of CD8 T cells in mycobacterial infection and tuberculosis.
Klein
M R
MR
Tuberculosis Research Programme, Medical Research Council Laboratories, Fajara, BANJUL, Gambia, West Africa. mklein@mrc.gm
Smith
S M
SM
Hammond
A S
AS
Ogg
G S
GS
King
A S
AS
Vekemans
J
J
Jaye
A
A
Lukey
P T
PT
McAdam
K P
KP
D000217:Acyltransferases; D000465:Algorithms; D020816:Amino Acid Motifs; D000942:Antigens, Bacterial / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015797:HLA-B35 Antigen / Q000276:immunology*; D006801:Humans; D007372:Interferons / Q000096:biosynthesis; D008264:Macrophages / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D015797:HLA-B35 Antigen; D010455:Peptides; D007372:Interferons; D000217:Acyltransferases; C119774:antigen 85C, Mycobacterium tuberculosis