Expression of Epstein-Barr virus-encoded growth-transformation-associated proteins in lymphoproliferations of bone-marrow transplant recipients.
The expression of Epstein-Barr virus (EBV)-encoded, growth-transformation-associated proteins was studied in lymphoproliferations of 9 allogeneic bone-marrow transplant (BMT) recipients. Immunoblots of cell lysates were probed with polyspecific and monospecific antisera directed against EBNA 1, 2, 3 and 6, and the membrane protein LMP. All tumors expressed EBNA 1 and LMP. EBNA 2 was detected in the tumors of 8 patients, and EBNA 3 and 6 in the tumors of 5 patients. The LMP regulatory sequences, 5' of the LMP gene, were totally unmethylated in all 7 cases, while the coding sequences of LMP and EBNA 2 were more methylated in CpG dinucleotides. EBV-transformed lymphoblastoid cell lines (LCL) express EBNA 1 to 6 and LMP; in contrast, Burkitt lymphomas express only EBNA 1. In vitro experiments have shown that EBNA 2, 3 and LMP can generate targets for cytotoxic T cells (CTL). These combined observations are consistent with the hypothesis that the EBV-associated lymphoproliferative disease of the BMT recipients escapes CTL-mediated rejection due to the failure of host immunosurveillance rather than to the down-regulation of immunogenic EBV-encoded antigens.
Gratama
J W
JW
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Zutter
M M
MM
Minarovits
J
J
Oosterveer
M A
MA
Thomas
E D
ED
Klein
G
G
Ernberg
I
I
D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000032:analysis* / Q000235:genetics; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D004279:DNA, Viral / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000378:metabolism / Q000382:microbiology*; D008745:Methylation; D014763:Viral Matrix Proteins
D000956:Antigens, Viral; D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins