Engagement of CD40 antigen with soluble CD40 ligand up-regulates peptide transporter expression and restores endogenous processing function in Burkitt's lymphoma cells.
Cells from the EBV-associated tumor, Burkitt's lymphoma (BL), are known to be highly inefficient at endogenous processing of class I-restricted CTL epitopes due to a consistent loss of peptide transporters (TAP) and MHC expression. We investigated the potential of CD40 engagement to up-regulate the expression of class I-processing genes and to enhance the immunogenicity of these malignant cells toward EBV-specific CTLs. Here we show that engagement of CD40 Ag with soluble CD40 ligand (CD40L) up-regulates TAP-1 and HLA class I expression on BL cells. More importantly, analysis of the Ag-processing function, using a recombinant vaccinia virus to transiently express the EBV nuclear Ags, revealed that CD40L-treated BL cells consistently processed endogenously synthesized viral Ags for recognition by HLA class I-restricted, virus-specific CTLs. These findings raise the possibility that CD40L treatment of tumor cells might be exploited in immunotherapeutic protocols.
Khanna
R
R
EBV Unit, Queensland Institute of Medical Research, Herston, Australia. rajivK@qimr.edu.au
Cooper
L
L
Kienzle
N
N
Moss
D J
DJ
Burrows
S R
SR
Khanna
K K
KK
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D017951:Antigen Presentation; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D006680:HLA Antigens / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016056:Immunodominant Epitopes / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D019013:CD40 Antigens; D019309:Epstein-Barr Virus Nuclear Antigens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D008024:Ligands; D008562:Membrane Glycoproteins; C073119:TAP1 protein, human; D023201:CD40 Ligand