MHC class I and class II presentation of tumor antigen in retrovirally and adenovirally transduced dendritic cells.
The unique antigen-presenting capabilities of dendritic cells (DCs) make them an attractive means with which to initiate an antitumor immune response. Using DCs transduced with tumor antigens for immunotherapy has several theoretical advantages over peptide-pulsed DCs including the possibility that transduced DCs are capable of presenting epitopes on both class I and class II MHC molecules. To test this theory, we inserted the human tumor antigen gp100 into mouse DCs transgenic for HLA-DRbeta1*0401 using either adenoviral vector or a VSV-G pseudotyped retroviral vector. DCs transduced with tumor antigen were able to be recognized by both a murine CD8(+) T-cell clone and a murine CD4(+) T-cell line in a cytokine release assay, thereby demonstrating presentation of both MHC class I and class II gp100 epitopes. This study describes the simultaneous presentation of a tumor-associated antigen to both CD4(+) and CD8(+) T cells and lends support to the use of gene-modified DCs as a means to initiate both CD4(+) and CD8(+) antitumor responses.
Sloan
J Mark
JM
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Kershaw
Michael H
MH
Touloukian
Christopher E
CE
Lapointe
Rejean
R
Robbins
Paul F
PF
Restifo
Nicholas P
NP
Hwu
Patrick
P
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D049452:Green Fluorescent Proteins; D006684:HLA-DR Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D008164:Luminescent Proteins / Q000235:genetics; D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000276:immunology; D014162:Transfection
D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D007371:Interferon-gamma