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The secreted Mycobacterium tuberculosis 10-kDa culture filtrate protein (CFP)10 is a potent T cell Ag that is recognized by a high percentage of persons infected with M. tuberculosis. We determined the molecular basis for this widespread recognition by identifying and characterizing a 15-mer peptide, CFP10(71-85), that elicited IFN-gamma production and CTL activity by both CD4(+) and CD8(+) T cells from persons expressing multiple MHC class II and class I molecules, respectively. CFP10(71-85) contained at least two epitopes, one of 10 aa (peptide T1) and another of 9 aa (peptide T6). T1 was recognized by CD4(+) cells in the context of DRB1*04, DR5*0101, and DQB1*03, and by CD8(+) cells of A2(+) donors. T6 elicited responses by CD4(+) cells in the context of DRB1*04 and DQB1*03, and by CD8(+) cells of B35(+) donors. Deleting a single amino acid from the amino or carboxy terminus of either peptide markedly reduced IFN-gamma production, suggesting that they are minimal epitopes for both CD4(+) and CD8(+) cells. As far as we are aware, these are the shortest microbial peptides that have been found to elicit responses by both T cell subpopulations. The capacity of CFP10(71-85) to stimulate IFN-gamma production and CTL activity by CD4(+) and CD8(+) cells from persons expressing a spectrum of MHC molecules suggests that this peptide is an excellent candidate for inclusion in a subunit antituberculosis vaccine.

Original publication

DOI

10.4049/jimmunol.173.3.1966

Type

Journal article

Journal

J Immunol

Publication Date

01/08/2004

Volume

173

Pages

1966 - 1977

Keywords

Alleles, Amino Acid Substitution, Antigens, Bacterial, Bacterial Proteins, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Epitopes, HLA Antigens, HLA-DQ Antigens, HLA-DQ beta-Chains, HLA-DR Antigens, HLA-DRB1 Chains, Humans, Interferon-gamma, Mycobacterium tuberculosis, Peptide Fragments, Sequence Deletion, T-Cell Antigen Receptor Specificity, Tuberculosis Vaccines