Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP-Binding Cassette Transporters / biosynthesis*
-
Antigen Presentation*
-
Burkitt Lymphoma / immunology*
-
Burkitt Lymphoma / metabolism
-
CD40 Antigens / metabolism*
-
CD40 Ligand
-
Epstein-Barr Virus Nuclear Antigens / metabolism
-
HLA Antigens / biosynthesis
-
Herpesvirus 4, Human / immunology
-
Histocompatibility Antigens Class I / biosynthesis
-
Humans
-
Immunodominant Epitopes / metabolism
-
Ligands
-
Membrane Glycoproteins / metabolism*
-
Solubility
-
T-Lymphocytes, Cytotoxic / immunology
-
T-Lymphocytes, Cytotoxic / metabolism
-
T-Lymphocytes, Cytotoxic / virology
-
Tumor Cells, Cultured
-
Up-Regulation / immunology*
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP-Binding Cassette Transporters
-
CD40 Antigens
-
Epstein-Barr Virus Nuclear Antigens
-
HLA Antigens
-
Histocompatibility Antigens Class I
-
Immunodominant Epitopes
-
Ligands
-
Membrane Glycoproteins
-
TAP1 protein, human
-
CD40 Ligand