Engagement of CD40 antigen with soluble CD40 ligand up-regulates peptide transporter expression and restores endogenous processing function in Burkitt's lymphoma cells.

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.

• Authors: R Khanna, L Cooper, N Kienzle, D J Moss, S R Burrows, K K Khanna
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 159 Issue 12 Pg. 5782-5 (Dec 15 1997) ISSN: 0022-1767 [Print] United States
• PMID: 9550373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 2
• ATP-Binding Cassette Transporters (biosynthesis)
• Antigen Presentation
• Burkitt Lymphoma (immunology, 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, metabolism, virology)
• Tumor Cells, Cultured
• Up-Regulation (immunology)