Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles

Homayoun Shams, Peter Klucar, Stephen Weis, Ajit Lalvani, Patrick K. Moonan, Hassan Safi, Benjamin Wizel, Katie Ewer, Gerald T. Nepom, David M. Lewinsohn, Peter Andersen, Peter F. Barnes

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Abstract

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, CFP1071-85, that elicited IFN-γ production and CTL activity by both CD4+ and CD8+ T cells from persons expressing multiple MHC class II and class I molecules, respectively. CFP1071-85 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-γ 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 CFP1071-85 to stimulate IFN-γ 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 languageEnglish
Pages (from-to)1966-1977
Number of pages12
JournalJournal of Immunology
Volume173
Issue number3
DOIs
StatePublished - 1 Aug 2004

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Mycobacterium tuberculosis
Alleles
T-Lymphocytes
Peptides
Epitopes
Subunit Vaccines
varespladib methyl
Amino Acids

Cite this

Shams, Homayoun ; Klucar, Peter ; Weis, Stephen ; Lalvani, Ajit ; Moonan, Patrick K. ; Safi, Hassan ; Wizel, Benjamin ; Ewer, Katie ; Nepom, Gerald T. ; Lewinsohn, David M. ; Andersen, Peter ; Barnes, Peter F. / Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles. In: Journal of Immunology. 2004 ; Vol. 173, No. 3. pp. 1966-1977.
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abstract = "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, CFP1071-85, that elicited IFN-γ production and CTL activity by both CD4+ and CD8+ T cells from persons expressing multiple MHC class II and class I molecules, respectively. CFP1071-85 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-γ 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 CFP1071-85 to stimulate IFN-γ 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.",
author = "Homayoun Shams and Peter Klucar and Stephen Weis and Ajit Lalvani and Moonan, {Patrick K.} and Hassan Safi and Benjamin Wizel and Katie Ewer and Nepom, {Gerald T.} and Lewinsohn, {David M.} and Peter Andersen and Barnes, {Peter F.}",
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Shams, H, Klucar, P, Weis, S, Lalvani, A, Moonan, PK, Safi, H, Wizel, B, Ewer, K, Nepom, GT, Lewinsohn, DM, Andersen, P & Barnes, PF 2004, 'Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles', Journal of Immunology, vol. 173, no. 3, pp. 1966-1977. https://doi.org/10.4049/jimmunol.173.3.1966

Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles. / Shams, Homayoun; Klucar, Peter; Weis, Stephen; Lalvani, Ajit; Moonan, Patrick K.; Safi, Hassan; Wizel, Benjamin; Ewer, Katie; Nepom, Gerald T.; Lewinsohn, David M.; Andersen, Peter; Barnes, Peter F.

In: Journal of Immunology, Vol. 173, No. 3, 01.08.2004, p. 1966-1977.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Characterization of a Mycobacterium tuberculosis peptide that is recognized by human CD4+ and CD8+ T cells in the context of multiple HLA alleles

AU - Shams, Homayoun

AU - Klucar, Peter

AU - Weis, Stephen

AU - Lalvani, Ajit

AU - Moonan, Patrick K.

AU - Safi, Hassan

AU - Wizel, Benjamin

AU - Ewer, Katie

AU - Nepom, Gerald T.

AU - Lewinsohn, David M.

AU - Andersen, Peter

AU - Barnes, Peter F.

PY - 2004/8/1

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AB - 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, CFP1071-85, that elicited IFN-γ production and CTL activity by both CD4+ and CD8+ T cells from persons expressing multiple MHC class II and class I molecules, respectively. CFP1071-85 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-γ 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 CFP1071-85 to stimulate IFN-γ 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.

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