Immunization with a carbohydrate mimicking peptide augments tumor-specificcellular responses

The metastatic potential of some tumor cells is associated with the express ion of the neolactoseries antigens sialyl-Lewis x (sLex) and sialyl-Lewis a (sLea) as they are ligands for selectins. We have recently shown that pept ide mimetics of these antigens can potentiate IgG2a antibodies, which are a ssociated with a T(h)1-type cellular response. As L-selectin is preferentia lly expressed on CD4(+) T(h)1 and CD8(+) T cell populations, specific induc tion of these phenotypes could augment a response to L-selectin ligand-expr essing tumor cells. Here we demonstrate that immunization with a multiple a ntigen peptide (MAP) mimetic of sugar constituents of neolactoseries antige ns induces a MHC-dependent peptide-specific cellular response that triggers IFN-gamma production upon peptide stimulation, correlating with IgG2a indu ction. Surprisingly, T lymphocytes from peptide-immunized animals were acti vated in vitro by sLex, also triggering IFN-gamma production in a MHC-depen dent manner. Stimulation by peptide or carbohydrate resulted in loss of L-s electin on CD4(+) T cells confirming a TO phenotype. We also observed an en hancement in cytotoxic T lymphocyte (CTL) activity in vitro against sLex-ex pressing Meth A cells using effector cells from Meth A-primed/peptide-boost ed animals. CTL activity was inhibited by both anti-MHC class I and anti-L- selectin antibodies. These results further support a role for L-selectin in tumor rejection along with the engagement by the TCR for most likely proce ssed tumor-associated glycopeptides, focusing on peptide mimetics as a mean s to induce carbohydrate reactive cellular responses.