Down-Regulation of Class I HLA Antigens and of the Epstein--Barr Virus-Encoded Latent Membrane Protein in Burkitt Lymphoma Lines

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 13; pp. 4567 - 4571
• Main Authors: Masucci, M. G., Torsteinsdottir, S., Colombani, J., Brautbar, C., Klein, E., Klein, G.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.07.1987; National Acad Sciences
• Subjects: Antigens; Antigens, Neoplasm - biosynthesis; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; B lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; Blasts; Burkitt lymphoma; Burkitt Lymphoma - genetics; Burkitt Lymphoma - immunology; Burkitt's lymphoma; Cell Line; Cell lines; Cytotoxicity, Immunologic; Down regulation; Epstein-Barr virus; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Herpesvirus 4, Human - immunology; histocompatibility antigen HLA; HLA antigens; HLA Antigens - biosynthesis; HLA Antigens - genetics; HLA Antigens - immunology; HLA-A Antigens; HLA-A11 Antigen; Humans; Immunologic Surveillance; Lymphocyte Activation; Lymphocytes; man; membrane proteins; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Phenotype; Phenotypes; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Tissue, organ and graft immunology; Viral Proteins - biosynthesis; Viral Proteins - genetics; Human; Membrane protein; Herpesviridae; Major histocompatibility system; Burkitt lymphoma; Epstein Barr virus; HLA»-System; Gene expression; Infection; Virus; Antigen; Viral disease; Established cell line; Inhibition; γ-Herpesvirinae
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.13.4567

Epstein-Barr virus (EBV)-carrying Burkitt lymphoma (BL) cells are relatively or completely resistant to the lytic effect of major histocompatibility complex class I HLA antigen-restricted cytotoxic T lymphocytes (CTLs) generated by stimulating lymphocytes of EBV-seropositive donors with the autologous EBV-transformed lymphoblastoid cell line (LCL). We previously found that EBV-negative and EBV-carrying BL lines derived from HLA-A11-positive donors were not only resistant to lysis by the HLA-A11-restricted CTL generated by stimulation with the autologous LCL, but also to HLA-A11-specific CTL derived from lymphocytes of an EBV-seronegative donor stimulated with an allogeneic LCL. Using the same and additional cell lines, we now show that the CTL resistance of the BL lines is probably due to a selective down-regulation of HLA-A11. We also show that the EBV-encoded latent membrane protein is expressed at a lower level in the EBV-carrying BL lines than in EBV-transformed LCLs. Only one of eight in vitro EBV-converted BL lines that shifted to a more LCL-like growth pattern expressed LMP at a high level. This line also reexpressed the HLA-A11 antigen that was undetectable in its EBV-negative progenitor. Our findings suggest that the typical BL cell phenotype is associated with low expression of both proteins.