CD40 activation enhances the magnitude of cellular immune responses against p53 but not the avidity of the effectors |
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Authors: | Lorne F Erdile Darlene Smith |
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Institution: | (1) Virogenetics/Aventis Pasteur, 465 Jordan Road, Troy NY 12180, USA, US |
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Abstract: | Engagement of CD40 on the surface of antigen-presenting cells (APC) has been shown to substitute for T cell help in activating
APC to stimulate cytotoxic T lymphocytes (CTL). We explored whether this powerful non-specific signal could enhance the CTL
response to a self epitope from a tumor-associated antigen. We immunized mice with a lipopeptide covering the H-2Kd-restricted epitope, amino acids 232–240 of murine wild-type p53, followed by treatment with an activating anti-CD40 monoclonal
antibody. Anti-CD40 antibody, given subcutaneously or intravenously, significantly enhanced effector activity against targets
pulsed with non-lipidated 232–240 nonamer epitope peptide, as assessed both by a CTL lysis assay and an enzyme-linked immunospot
(ELISPOT) assay for interferon-γ-secreting cells. However, despite this enhancement, we could not detect activity against
targets expressing p53 endogenously by either assay. This most likely reflects the low avidity of the effectors as determined
by a titration of peptide on the target cells. The implications of this work for cancer immunotherapy based on specific responses
directed against tumor-associated antigens are discussed.
Received: 28 March 2000 / Accepted: 6 June 2000 |
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Keywords: | p53 Cellular immune response CD40 |
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