Proteasomal targeting and minigene repetition improve cell-surface presentation of a transfected, modified melanoma tumour antigen

TY - JOUR

T1 - Proteasomal targeting and minigene repetition improve cell-surface presentation of a transfected, modified melanoma tumour antigen

AU - Rasmussen, A B

AU - Zocca, M-B

AU - Bonefeld, C M

AU - von Essen, M

AU - Lauritsen, J P

AU - Tomra, S

AU - Odum, N

AU - Geisler, C

N1 - Keywords: Amino Acid Sequence; Antigen Presentation; Antigens, Neoplasm; Blotting, Western; Cancer Vaccines; Cell Line; Cysteine Endopeptidases; Cytotoxicity Tests, Immunologic; Epitopes; Humans; Melanoma; Molecular Sequence Data; Multienzyme Complexes; Neoplasm Proteins; Plasmids; Polymerase Chain Reaction; Proteasome Endopeptidase Complex; Repetitive Sequences, Nucleic Acid; T-Lymphocytes; Transfection; Vaccines, DNA

PY - 2004

Y1 - 2004

N2 - Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent on the density of specific major histocompatibility complex-peptide complexes on the surface of the antigen-presenting cell. In this study, we explored the cell-surface presentation of a substituted MART-1 peptide encoded by transfected minigenes. We investigated the potential of proteasomal targeting compared to non-proteasomal targeting of the epitope to increase its cell-surface presentation. Furthermore, we explored the potential of incorporating multiple minigenes instead of one to increase cell-surface presentation. We show that both proteasomal targeting and repetition of the minigene increase cell-surface presentation of the epitope and propose both these approaches as potential strategies in DNA vaccines to increase MART-1-specific T-cell activation.

AB - Melanoma antigen recognized by T cell 1 (MART-1) is regarded as a candidate peptide for vaccination against malignant melanoma, and it is of importance to develop strategies to improve the vaccine-elicited T-cell activation towards MART-1. T-cell activation is, among other determinants, dependent on the density of specific major histocompatibility complex-peptide complexes on the surface of the antigen-presenting cell. In this study, we explored the cell-surface presentation of a substituted MART-1 peptide encoded by transfected minigenes. We investigated the potential of proteasomal targeting compared to non-proteasomal targeting of the epitope to increase its cell-surface presentation. Furthermore, we explored the potential of incorporating multiple minigenes instead of one to increase cell-surface presentation. We show that both proteasomal targeting and repetition of the minigene increase cell-surface presentation of the epitope and propose both these approaches as potential strategies in DNA vaccines to increase MART-1-specific T-cell activation.

M3 - Journal article

C2 - 14871300

SN - 0300-9475

VL - 59

SP - 220

EP - 227

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

IS - 2

ER -