An HLA-A2-restricted T-cell Epitope Mapped to the BNLF2a Immune Evasion Protein of Epstein-Barr Virus That Inhibits TAP

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2009 Jan 9

PMID 19129449

Citations 8

Authors

Melissa J Bell

Rachel J M Abbott

Nathan P Croft

Andrew D Hislop

Scott R Burrows

Affiliations

Soon will be listed here.

Abstract

The early lytic cycle protein of Epstein-Barr virus (EBV), BNLF2a, has recently been shown to play a critical role in immune evasion by inhibiting the peptide transporter associated with antigen processing (TAP), thereby blocking antigen-specific CD8(+) T-cell recognition of many lytic cycle antigens. Surprisingly, we now show that a peptide ((50)VLFGLLCLL(58)) from the hydrophobic C-terminal region of this small (60-amino-acid) EBV protein is efficiently presented by the common class I allele HLA-A2 for recognition by cytotoxic T lymphocytes. The mechanism for this unexpected finding was revealed by experiments showing that this epitope is processed and presented independently of TAP.

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References

Khanna R, Burrows S . Role of cytotoxic T lymphocytes in Epstein-Barr virus-associated diseases. Annu Rev Microbiol. 2000; 54:19-48. DOI: 10.1146/annurev.micro.54.1.19. View

Burrows J, Wynn K, Tynan F, Archbold J, Miles J, Bell M . The impact of HLA-B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV. Eur J Immunol. 2007; 37(4):946-53. DOI: 10.1002/eji.200636588. View

Tigges M, Leng S, Johnson D, Burke R . Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2-infected fibroblasts after treatment with IFN-gamma or when virion host shutoff functions are disabled. J Immunol. 1996; 156(10):3901-10. View

Fruh K, Ahn K, Djaballah H, SEMPE P, van Endert P, Tampe R . A viral inhibitor of peptide transporters for antigen presentation. Nature. 1995; 375(6530):415-8. DOI: 10.1038/375415a0. View

Lehner P, Karttunen J, Wilkinson G, Cresswell P . The human cytomegalovirus US6 glycoprotein inhibits transporter associated with antigen processing-dependent peptide translocation. Proc Natl Acad Sci U S A. 1997; 94(13):6904-9. PMC: 21257. DOI: 10.1073/pnas.94.13.6904. View

Pamer E, Cresswell P . Mechanisms of MHC class I--restricted antigen processing. Annu Rev Immunol. 1998; 16:323-58. DOI: 10.1146/annurev.immunol.16.1.323. View

Lautscham G, Mayrhofer S, Taylor G, Haigh T, Leese A, Rickinson A . Processing of a multiple membrane spanning Epstein-Barr virus protein for CD8(+) T cell recognition reveals a proteasome-dependent, transporter associated with antigen processing-independent pathway. J Exp Med. 2001; 194(8):1053-68. PMC: 2193515. DOI: 10.1084/jem.194.8.1053. View

Rowe M, Glaunsinger B, van Leeuwen D, Zuo J, Sweetman D, Ganem D . Host shutoff during productive Epstein-Barr virus infection is mediated by BGLF5 and may contribute to immune evasion. Proc Natl Acad Sci U S A. 2007; 104(9):3366-71. PMC: 1805610. DOI: 10.1073/pnas.0611128104. View

Hislop A, Ressing M, van Leeuwen D, Pudney V, Horst D, Koppers-Lalic D . A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. J Exp Med. 2007; 204(8):1863-73. PMC: 2118677. DOI: 10.1084/jem.20070256. View

10.

Koppers-Lalic D, Reits E, Ressing M, Lipinska A, Abele R, Koch J . Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing. Proc Natl Acad Sci U S A. 2005; 102(14):5144-9. PMC: 555605. DOI: 10.1073/pnas.0501463102. View

11.

Ressing M, Keating S, van Leeuwen D, Koppers-Lalic D, Pappworth I, Wiertz E . Impaired transporter associated with antigen processing-dependent peptide transport during productive EBV infection. J Immunol. 2005; 174(11):6829-38. DOI: 10.4049/jimmunol.174.11.6829. View

12.

Burrows S, Silins S, Moss D, Khanna R, Misko I, Argaet V . T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen. J Exp Med. 1995; 182(6):1703-15. PMC: 2192251. DOI: 10.1084/jem.182.6.1703. View

13.

Yuan J, Cahir-McFarland E, Zhao B, Kieff E . Virus and cell RNAs expressed during Epstein-Barr virus replication. J Virol. 2006; 80(5):2548-65. PMC: 1395376. DOI: 10.1128/JVI.80.5.2548-2565.2006. View

14.

Pudney V, Leese A, Rickinson A, Hislop A . CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells. J Exp Med. 2005; 201(3):349-60. PMC: 2213038. DOI: 10.1084/jem.20041542. View

15.

Green K, Miles J, Tellam J, van Zuylen W, Connolly G, Burrows S . Potent T cell response to a class I-binding 13-mer viral epitope and the influence of HLA micropolymorphism in controlling epitope length. Eur J Immunol. 2004; 34(9):2510-9. DOI: 10.1002/eji.200425193. View

16.

Salter R, Cresswell P . Impaired assembly and transport of HLA-A and -B antigens in a mutant TxB cell hybrid. EMBO J. 1986; 5(5):943-9. PMC: 1166886. DOI: 10.1002/j.1460-2075.1986.tb04307.x. View

17.

Shimizu Y, Geraghty D, Koller B, Orr H, Demars R . Transfer and expression of three cloned human non-HLA-A,B,C class I major histocompatibility complex genes in mutant lymphoblastoid cells. Proc Natl Acad Sci U S A. 1988; 85(1):227-31. PMC: 279517. DOI: 10.1073/pnas.85.1.227. View

18.

Tellam J, Connolly G, Green K, Miles J, Moss D, Burrows S . Endogenous presentation of CD8+ T cell epitopes from Epstein-Barr virus-encoded nuclear antigen 1. J Exp Med. 2004; 199(10):1421-31. PMC: 2211806. DOI: 10.1084/jem.20040191. View

19.

Ahn K, Gruhler A, Galocha B, Jones T, Wiertz E, Ploegh H . The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP. Immunity. 1997; 6(5):613-21. DOI: 10.1016/s1074-7613(00)80349-0. View

20.

Falk K, Rotzschke O, Stevanovic S, Jung G, Rammensee H . Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991; 351(6324):290-6. DOI: 10.1038/351290a0. View