International Immunology, Vol. 13, No. 11, 1361-1365,
November 2001
© 2001 Japanese Society for Immunology
Immunization with a carbohydrate mimicking peptide augments tumor-specific cellular responses
Department of Pathology and Laboratory Medicine, University of Pennsylvania, and
1 The Wistar Institute, Philadelphia, PA 19104, USA
Correspondence to: T. Kieber-Emmons
The metastatic potential of some tumor cells is associated with the expression of the neolactoseries antigens sialyl-Lewis x (sLex) and sialyl-Lewis a (sLea) as they are ligands for selectins. We have recently shown that peptide mimetics of these antigens can potentiate IgG2a antibodies, which are associated with a Th1-type cellular response. As L-selectin is preferentially expressed on CD4+ Th1 and CD8+ T cell populations, specific induction of these phenotypes could augment a response to L-selectin ligand-expressing tumor cells. Here we demonstrate that immunization with a multiple antigen peptide (MAP) mimetic of sugar constituents of neolactoseries antigens induces a MHC-dependent peptide-specific cellular response that triggers IFN-
production upon peptide stimulation, correlating with IgG2a induction. Surprisingly, T lymphocytes from peptide-immunized animals were activated in vitro by sLex, also triggering IFN- production in a MHC-dependent manner. Stimulation by peptide or carbohydrate resulted in loss of L-selectin on CD4+ T cells confirming a Th1 phenotype. We also observed an enhancement in cytotoxic T lymphocyte (CTL) activity in vitroagainst sLex-expressing Meth A cells using effector cells from Meth A-primed/peptide-boosted animals. CTL activity was inhibited by both anti-MHC class I and anti-L-selectin antibodies. These results further support a role forL-selectin in tumor rejection along with the engagement by the TCR for most likely processedtumor-associated glycopeptides, focusing on peptide mimetics as a means to induce carbohydrate reactive cellular responses.
Keywords: cancer vaccine, carbohydrate, L-selectin, Meth A cells, peptide mimeotope
Transmitting editor: M. Miyasaka
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  B. Monzavi-Karbassi, P. Luo, F. Jousheghany, M. Torres-Quinones, G. Cunto-Amesty, C. Artaud, and T. Kieber-Emmons A Mimic of Tumor Rejection Antigen-Associated Carbohydrates Mediates an Antitumor Cellular Response Cancer Res., March 15, 2004; 64(6): 2162 - 2166. [Abstract] [Full Text] [PDF]
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