scholarly journals CD4+ T-Cell Responses to Epstein-Barr Virus Nuclear Antigen EBNA1 in Chinese Populations Are Highly Focused on Novel C-Terminal Domain-Derived Epitopes

2006 ◽  
Vol 80 (16) ◽  
pp. 8263-8266 ◽  
Author(s):  
C. W. Tsang ◽  
X. Lin ◽  
N. H. Gudgeon ◽  
G. S. Taylor ◽  
H. Jia ◽  
...  

ABSTRACT Epstein-Barr virus nuclear antigen EBNA1, the one viral protein uniformly expressed in nasopharyngeal carcinoma (NPC), represents a prime target for T-cell-based immunotherapy. However, little is known about the EBNA1 epitopes, particularly CD4 epitopes, presented by HLA alleles in Chinese people, the group at highest risk for NPC. We analyzed the CD4+ T-cell responses to EBNA1 in 78 healthy Chinese donors and found marked focusing on a small number of epitopes in the EBNA1 C-terminal region, including a DP5-restricted epitope that was recognized by almost half of the donors tested and elicited responses able to recognize EBNA1-expressing, DP5-positive target cells.

2005 ◽  
Vol 79 (8) ◽  
pp. 4896-4907 ◽  
Author(s):  
H. M. Long ◽  
T. A. Haigh ◽  
N. H. Gudgeon ◽  
A. M. Leen ◽  
C.-W. Tsang ◽  
...  

ABSTRACT There is considerable interest in the potential of Epstein-Barr virus (EBV) latent antigen-specific CD4+ T cells to act as direct effectors controlling EBV-induced B lymphoproliferations. Such activity would require direct CD4+ T-cell recognition of latently infected cells through epitopes derived from endogenously expressed viral proteins and presented on the target cell surface in association with HLA class II molecules. It is therefore important to know how often these conditions are met. Here we provide CD4+ epitope maps for four EBV nuclear antigens, EBNA1, -2, -3A, and -3C, and establish CD4+ T-cell clones against 12 representative epitopes. For each epitope we identify the relevant HLA class II restricting allele and determine the efficiency with which epitope-specific effectors recognize the autologous EBV-transformed B-lymphoblastoid cell line (LCL). The level of recognition measured by gamma interferon release was consistent among clones to the same epitope but varied between epitopes, with values ranging from 0 to 35% of the maximum seen against the epitope peptide-loaded LCL. These epitope-specific differences, also apparent in short-term cytotoxicity and longer-term outgrowth assays on LCL targets, did not relate to the identity of the source antigen and could not be explained by the different functional avidities of the CD4+ clones; rather, they appeared to reflect different levels of epitope display at the LCL surface. Thus, while CD4+ T-cell responses are detectable against many epitopes in EBV latent proteins, only a minority of these responses are likely to have therapeutic potential as effectors directly recognizing latently infected target cells.


2008 ◽  
Vol 123 (12) ◽  
pp. 2824-2831 ◽  
Author(s):  
Kevin N. Heller ◽  
Frida Arrey ◽  
Peter Steinherz ◽  
Carol Portlock ◽  
Amy Chadburn ◽  
...  

2007 ◽  
Vol 81 (9) ◽  
pp. 4904-4908 ◽  
Author(s):  
Florian Bihl ◽  
Murli Narayan ◽  
John V. Chisholm ◽  
Leah M. Henry ◽  
Todd J. Suscovich ◽  
...  

ABSTRACT The cellular immunity against Kaposi's sarcoma-associated herpesvirus (KSHV) is poorly characterized and has not been compared to T-cell responses against other human herpesviruses. Here, novel and dominant targets of KSHV-specific cellular immunity are identified and compared to T cells specific for lytic and latent antigens in a second human gammaherpesvirus, Epstein-Barr virus. The data identify a novel HLA-B57- and HLA-B58-restricted epitope in the Orf57 protein and show consistently close parallels in immune phenotypes and functional response patterns between cells targeting lytic or latent KSHV- and EBV-encoded antigens, suggesting common mechanisms in the induction of these responses.


2008 ◽  
Vol 123 (5) ◽  
pp. 1100-1107 ◽  
Author(s):  
Debora Martorelli ◽  
Karim Houali ◽  
Laura Caggiari ◽  
Emanuela Vaccher ◽  
Luigi Barzan ◽  
...  

2005 ◽  
Vol 66 (9) ◽  
pp. 938-949 ◽  
Author(s):  
Marion Subklewe ◽  
Kathrin Sebelin ◽  
Andrea Block ◽  
Antje Meier ◽  
Anna Roukens ◽  
...  

2011 ◽  
Vol 7 (12) ◽  
pp. e1002455 ◽  
Author(s):  
Jianmin Zuo ◽  
Wendy A. Thomas ◽  
Tracey A. Haigh ◽  
Leah Fitzsimmons ◽  
Heather M. Long ◽  
...  

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