Microbial HSPs (heat-shock proteins) are implicated in the induction of the innate and adaptive arms of the immune response. We set out to determine whether peptides complexed with HSP70 generate efficient CTL (cytolytic T-lymphocyte) responses. Human dendritic cells pulsed with peptide-loaded microbial HSP70 complexes generate potent antigen-specific CTL responses. Using fluorescence anisotropy, we have calculated the peptide-binding affinity of mycobacterial HSP70 (KD=14 μM) and show that 120 pM HSP70-bound peptide is sufficient to generate a peptide-specific CTL response that is four orders of magnitude more efficient than the peptide alone. Through the generation of mycobacterial HSP70 truncations, we find that the minimal 136 amino acid, mycobacterial HSP70 peptide-binding domain is sufficient to generate CTL responses. The design of an HSP70 mutant, in which the peptide-binding site of HSP70 is filled with a bulky hydrophobic residue, leads to a large decrease in the peptide-binding affinity. This mutant HSP70 retains stimulatory capacity but is unable to generate CTL and has separated antigen delivery from immunostimulation of dendritic cells.
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August 2004
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Conference Article|
August 01 2004
Peptides complexed with the protein HSP70 generate efficient human cytolytic T-lymphocyte responses
B. Javid;
B. Javid
1
*Division of Immunology, Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2XY, U.K.
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P.A. MacAry;
P.A. MacAry
1
*Division of Immunology, Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2XY, U.K.
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W. Oehlmann;
W. Oehlmann
†Lionex Diagnostics and Therapeutics GmbH, Braunschweig, Germany
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M. Singh;
M. Singh
†Lionex Diagnostics and Therapeutics GmbH, Braunschweig, Germany
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P.J. Lehner
P.J. Lehner
2
*Division of Immunology, Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2XY, U.K.
2To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
April 16 2004
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 The Biochemical Society
2004
Biochem Soc Trans (2004) 32 (4): 622–625.
Article history
Received:
April 16 2004
Citation
B. Javid, P.A. MacAry, W. Oehlmann, M. Singh, P.J. Lehner; Peptides complexed with the protein HSP70 generate efficient human cytolytic T-lymphocyte responses. Biochem Soc Trans 1 August 2004; 32 (4): 622–625. doi: https://doi.org/10.1042/BST0320622
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