Proteasome inhibitors reconstitute the presentation of cytotoxic T-cell epitopes in Epstein-Barr virus-associated tumors

2002 ◽  
Vol 101 (6) ◽  
pp. 532-538 ◽  
Author(s):  
Riccardo Gavioli ◽  
Simona Vertuani ◽  
Maria G. Masucci
1994 ◽  
Vol 75 (9) ◽  
pp. 2489-2493 ◽  
Author(s):  
S. R. Burrows ◽  
J. Gardner ◽  
R. Khanna ◽  
T. Steward ◽  
D. J. Moss ◽  
...  

1992 ◽  
Vol 22 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Ann Apolloni ◽  
Denis Moss ◽  
Robyn Stumm ◽  
Scott Burrows ◽  
Andreus Suhrbier ◽  
...  

2002 ◽  
Vol 160 (5) ◽  
pp. 1839-1845 ◽  
Author(s):  
Qian Tao ◽  
Jie Yang ◽  
He Huang ◽  
Lode J. Swinnen ◽  
Richard F. Ambinder

1982 ◽  
Vol 156 (6) ◽  
pp. 1854-1859 ◽  
Author(s):  
S L Wee ◽  
L K Chen ◽  
G Strassmann ◽  
F H Bach

We report here a class of helper cell-independent cytotoxic T cell (HITc) clones in man that can proliferate in response to antigenic stimulation as well as mediate cytotoxicity. HITc appear to be rare among clones derived from primary in vitro allosensitized culture, but constitute the majority of clones derived from cells sensitized to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines. The implications of the derivation and function of HITc clones are discussed.


1994 ◽  
Vol 57 (11) ◽  
pp. 1611-1616
Author(s):  
Myat T. Kyaw-Tanner ◽  
Donald Esmore ◽  
Scott R. Burrows ◽  
Elizabeth M. Benson ◽  
Tom B. Sculley

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Julio Alonso-Padilla ◽  
Esther M. Lafuente ◽  
Pedro A. Reche

Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt’s lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes. Such strategy relies on identifying conserved epitopes in conjunction with predictions of HLA presentation for T cell epitope selection and calculations of accessibility and flexibility for B cell epitope selection. The T cell component includes 14 CD8 T cell epitopes from early antigens and 4 CD4 T cell epitopes, targeted during the course of a natural infection and providing a population protection coverage of over 95% and 81.8%, respectively. The B cell component consists of 3 experimentally defined B cell epitopes from gp350 plus 4 predicted B cell epitopes from other EBV envelope glycoproteins, all mapping in flexible and solvent accessible regions. We discuss the rationale for the formulation and possible deployment of this epitope vaccine ensemble.


2004 ◽  
Vol 199 (10) ◽  
pp. 1421-1431 ◽  
Author(s):  
Judy Tellam ◽  
Geoff Connolly ◽  
Katherine J. Green ◽  
John J. Miles ◽  
Denis J. Moss ◽  
...  

Epstein-Barr virus (EBV)–encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type–dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I–restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8+ T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8+ T cell epitopes from EBNA1.


1994 ◽  
Vol 180 (6) ◽  
pp. 2335-2340 ◽  
Author(s):  
V P Argaet ◽  
C W Schmidt ◽  
S R Burrows ◽  
S L Silins ◽  
M G Kurilla ◽  
...  

To examine T cell receptor (TCR) diversity involved in the memory response to a persistent human pathogen, we determined nucleotide sequences encoding TCR-alpha and -beta chains from HLA-B8-restricted, CD8+ cytotoxic T cell clones specific for an immunodominant epitope (FLRGRAYGL) in Epstein-Barr virus (EBV) nuclear antigen 3. Herein, we show that identical TCR protein sequences are used by clones from each of four healthy unrelated virus carriers; a clone from a fifth varied conservatively at only two residues. This dominant selection of alpha and beta chain rearrangements suggest that a persistent viral infection can select for a highly focused memory response and indicates a strong bias in gene segment usage and recombination. A novel double-step semiquantitative polymerase chain reaction (PCR) procedure and direct sequencing of amplified TCR cDNA from fresh lymphocytes derived from three HLA-B8 individuals detected transcripts specific for the conserved beta chain in an EBV-seropositive donor but not in two seronegative donors. This report describes an unprecedented degree of conservation in TCR selected in response to a natural persistent infection.


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