title: Immunization with a carbohydrate mimicking peptide augments tumor-specific cellular responses.
abstract: 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-gamma production upon peptide stimulation, correlating with IgG2a induction. Surprisingly, T lymphocytes from peptide-immunized animals were activated in vitro by sLex, also triggering IFN-gamma 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 vitro against 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 for L-selectin in tumor rejection along with the engagement by the TCR for most likely processed tumor-associated glycopeptides, focusing on peptide mimetics as a means to induce carbohydrate reactive cellular responses.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: B
authors.initials: B
authors.lastname: Monzavi-Karbassi
authors.forename: G
authors.initials: G
authors.lastname: Cunto-Amesty
authors.forename: P
authors.initials: P
authors.lastname: Luo
authors.forename: S
authors.initials: S
authors.lastname: Shamloo
authors.forename: M
authors.initials: M
authors.lastname: Blaszcyk-Thurin
authors.forename: T
authors.initials: T
authors.lastname: Kieber-Emmons
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000008:administration & dosage* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis; D019041:L-Selectin / Q000032:analysis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D012513:Sarcoma, Experimental / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; C090410:CY 1503; D019496:Cancer Vaccines; D009844:Oligosaccharides; D010455:Peptides; D019041:L-Selectin; D007371:Interferon-gamma