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Title: Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery.
Austin Authors: Robson, Neil C;McAlpine, Tristan;Knights, Ashley J;Schnurr, Max;Shin, Amanda;Chen, Weisan;Maraskovsky, Eugene;Cebon, Jonathan S 
Affiliation: Ludwig Institute for Cancer Research, Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australia 3084, Australia
Issue Date: 29-Apr-2010
Publication information: Blood 2010; 116(2): 218-25
Abstract: The ability of dendritic cells (DCs) to cross-present protein tumor antigens to cytotoxic T lymphocytes (CTLs) underpins the success of therapeutic cancer vaccines. We studied cross-presentation of the cancer/testis antigen, NY-ESO-1, and the melanoma differentiation antigen, Melan-A by human DC subsets. Monocyte-derived DCs (MoDCs) efficiently cross-presented human leukocyte associated (HLA)-A2-restricted epitopes from either a formulated NY-ESO-1/ISCOMATRIX vaccine or when either antigen was mixed with ISCOMATRIX adjuvant. HLA-A2 epitope generation required endosomal acidification and was proteasome-independent for NY-ESO-1 and proteasome-dependent for Melan-A. Both MoDCs and CD1c(+) blood DCs cross-presented NY-ESO-1-specific HLA-A2(157-165)-, HLA-B7(60-72)-, and HLA-Cw3(92-100)-restricted epitopes when formulated as an NY-ESO-1/ISCOMATRIX vaccine, but this was limited when NY-ESO-1 and ISCOMATRIX adjuvant were added separately to the DC cultures. Finally, cross-presentation of NY-ESO-1(157-165)/HLA-A2, NY-ESO-1(60-72)/HLA-B7, and NY-ESO-1(92-100)/HLA-Cw3 epitopes was proteasome-dependent when formulated as immune complexes (ICs) but only proteasome-dependent for NY-ESO-1(60-72)/HLA-B7-restricted cross-presentation facilitated by ISCOMATRIX adjuvant. We demonstrate, for the first time, proteasome-dependent and independent cross-presentation of HLA-A-, B-, and C-restricted epitopes within the same full-length tumor antigen by human DCs. Our findings identify important differences in the capacities of human DC subsets to cross-present clinically relevant, full-length tumor antigens and how vaccine formulation impacts CTL responses in vivo.
Gov't Doc #: 20430956
DOI: 10.1182/blood-2009-10-249458
Type: Journal Article
Subjects: Antigen Presentation.immunology
Antigens, Neoplasm.immunology
Cancer Vaccines.immunology
Dendritic Cells.immunology
Drug Combinations
Epitopes, T-Lymphocyte.immunology
HLA-A Antigens.immunology
HLA-B Antigens.immunology
HLA-C Antigens.immunology
Histocompatibility Antigens Class I.immunology
Lymphocyte Activation.immunology
MART-1 Antigen
Neoplasm Proteins.immunology
Peptide Fragments.immunology
Proteasome Endopeptidase Complex.immunology
Appears in Collections:Journal articles

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