| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Cancer Research U.K. Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom
The CD4+ T cell response to EBV may have an important role in controlling virus-driven B lymphoproliferation because CD4+ T cell clones to a subset of EBV nuclear Ag (EBNA) epitopes can directly recognize virus-transformed lymphoblastoid cell lines (LCLs) in vitro and inhibit their growth. In this study, we used a panel of EBNA1, 2, 3A, and 3C-specific CD4+ T cell clones to study the route whereby endogenously expressed EBNAs access the HLA class II-presentation pathway. Two sets of results spoke against a direct route of intracellular access. First, none of the clones recognized cognate Ag overexpressed in cells from vaccinia vectors but did recognize Ag fused to an endo/lysosomal targeting sequence. Second, focusing on clones with the strongest LCL recognition that were specific for EBNA2- and EBNA3C-derived epitopes LCL recognition was unaffected by inhibiting autophagy, a postulated route for intracellular Ag delivery into the HLA class II pathway in LCL cells. Subsequently, using these same epitope-specific clones, we found that Ag-negative cells with the appropriate HLA-restricting allele could be efficiently sensitized to CD4+ T cell recognition by cocultivation with Ag-positive donor lines or by exposure to donor line-conditioned culture medium. Sensitization was mediated by a high m.w. antigenic species and required active Ag processing by recipient cells. We infer that intercellular Ag transfer plays a major role in the presentation of EBNA-derived CD4 epitopes by latently infected target cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Cancer Research U.K.
2 G.S.T. and H.M.L. contributed equally to the work.
3 Address correspondence and reprint requests to Prof. A. B. Rickinson, Cancer Research U.K. Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TT, U.K. E-mail address: A.B.Rickinson{at}bham.ac.uk
4 Abbreviations used in this paper: PTLD, posttransplant lymphoproliferative disease; LCL, lymphoblastoid cell line; EBNA, EBV nuclear Ag; 3-MA, 3-methyladenine; Ii, invariant chain; GAr, glycine-alanine repeat; moi, multiplicity of infection; MVA, modified vaccinia Ankara; CytC, cytochrome c; BL, Burkitt’s lymphoma.
This article has been cited by other articles:
|
|
 |
|
  H. M. Long, J. Zuo, A. M. Leese, N. H. Gudgeon, H. Jia, G. S. Taylor, and A. B. Rickinson CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus-transformed B cells Blood, July 23, 2009; 114(4): 807 - 815. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. L. Crotzer and J. S. Blum Autophagy and Its Role in MHC-Mediated Antigen Presentation J. Immunol., March 15, 2009; 182(6): 3335 - 3341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Harvey, T. E. Quan, B. J. Rudenga, R. M. Roman, J. Craft, and M. J. Mamula Editing Antigen Presentation: Antigen Transfer between Human B Lymphocytes and Macrophages Mediated by Class A Scavenger Receptors J. Immunol., September 15, 2008; 181(6): 4043 - 4051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Hislop, M. E. Ressing, D. van Leeuwen, V. A. Pudney, D. Horst, D. Koppers-Lalic, N. P. Croft, J. J. Neefjes, A. B. Rickinson, and E. J.H.J. Wiertz A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates J. Exp. Med., August 6, 2007; 204(8): 1863 - 1873. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
