Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition

Maaike E. Ressing; Daphne Van Leeuwen; Frank A.W. Verreck; Raquel Gomez; Bianca Heemskerk; Mireille Toebes; Maureen M. Mullen; Theodore S. Jardetzky; Richard Longnecker; Marco W. Schilham; Tom H.M. Ottenhoff; Jacques Neefjes; Ton N. Schumacher; Lindsey M. Hutt-Fletcher; Emmanuel J.H.J. Wiertz

doi:10.1073/pnas.2034960100

Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition

Maaike E. Ressing, Daphne Van Leeuwen, Frank A.W. Verreck, Raquel Gomez, Bianca Heemskerk, Mireille Toebes, Maureen M. Mullen, Theodore S. Jardetzky, Richard Longnecker, Marco W. Schilham, Tom H.M. Ottenhoff, Jacques Neefjes, Ton N. Schumacher, Lindsey M. Hutt-Fletcher, Emmanuel J.H.J. Wiertz^*

^*Corresponding author for this work

Microbiology-Immunology

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Abstract

Epstein-Barr virus (EBV) persists lifelong in infected hosts despite the presence of antiviral immunity. Many viral antigens are expressed during lytic infection. Thus, for EBV to spread, it must have evolved effective ways to evade immune recognition. Here, we report that HLA class II-restricted antigen presentation to T helper cells is hampered in the presence of the lytic-phase protein gp42. This interference with T cell activation involves association of gp42 with class II peptide complexes. Using HLA-DR tetramers, we identify a block in T cell receptor (TCR)-class II interactions imposed by gp42 as the underlying mechanism. EBV gp42 sterically clashes with TCR Vα-domains as visualized by superimposing the crystal structures for gp42-HLA-DR1 and TCR-MHC class II complexes. Blocking TCR recognition provides a previously undescribed strategy for viral immune evasion.

Original language	English (US)
Pages (from-to)	11583-11588
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	100
Issue number	20
DOIs	https://doi.org/10.1073/pnas.2034960100
State	Published - Sep 30 2003

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Ressing, M. E., Van Leeuwen, D., Verreck, F. A. W., Gomez, R., Heemskerk, B., Toebes, M., Mullen, M. M., Jardetzky, T. S., Longnecker, R., Schilham, M. W., Ottenhoff, T. H. M., Neefjes, J., Schumacher, T. N., Hutt-Fletcher, L. M., & Wiertz, E. J. H. J. (2003). Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition. Proceedings of the National Academy of Sciences of the United States of America, 100(20), 11583-11588. https://doi.org/10.1073/pnas.2034960100

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title = "Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition",

abstract = "Epstein-Barr virus (EBV) persists lifelong in infected hosts despite the presence of antiviral immunity. Many viral antigens are expressed during lytic infection. Thus, for EBV to spread, it must have evolved effective ways to evade immune recognition. Here, we report that HLA class II-restricted antigen presentation to T helper cells is hampered in the presence of the lytic-phase protein gp42. This interference with T cell activation involves association of gp42 with class II peptide complexes. Using HLA-DR tetramers, we identify a block in T cell receptor (TCR)-class II interactions imposed by gp42 as the underlying mechanism. EBV gp42 sterically clashes with TCR Vα-domains as visualized by superimposing the crystal structures for gp42-HLA-DR1 and TCR-MHC class II complexes. Blocking TCR recognition provides a previously undescribed strategy for viral immune evasion.",

author = "Ressing, {Maaike E.} and {Van Leeuwen}, Daphne and Verreck, {Frank A.W.} and Raquel Gomez and Bianca Heemskerk and Mireille Toebes and Mullen, {Maureen M.} and Jardetzky, {Theodore S.} and Richard Longnecker and Schilham, {Marco W.} and Ottenhoff, {Tom H.M.} and Jacques Neefjes and Schumacher, {Ton N.} and Hutt-Fletcher, {Lindsey M.} and Wiertz, {Emmanuel J.H.J.}",

year = "2003",

month = sep,

day = "30",

doi = "10.1073/pnas.2034960100",

language = "English (US)",

volume = "100",

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journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Ressing, ME, Van Leeuwen, D, Verreck, FAW, Gomez, R, Heemskerk, B, Toebes, M, Mullen, MM, Jardetzky, TS, Longnecker, R, Schilham, MW, Ottenhoff, THM, Neefjes, J, Schumacher, TN, Hutt-Fletcher, LM & Wiertz, EJHJ 2003, 'Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 20, pp. 11583-11588. https://doi.org/10.1073/pnas.2034960100

Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition. / Ressing, Maaike E.; Van Leeuwen, Daphne; Verreck, Frank A.W. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 20, 30.09.2003, p. 11583-11588.

Research output: Contribution to journal › Article › peer-review

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T1 - Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition

AU - Ressing, Maaike E.

AU - Van Leeuwen, Daphne

AU - Verreck, Frank A.W.

AU - Gomez, Raquel

AU - Heemskerk, Bianca

AU - Toebes, Mireille

AU - Mullen, Maureen M.

AU - Jardetzky, Theodore S.

AU - Longnecker, Richard

AU - Schilham, Marco W.

AU - Ottenhoff, Tom H.M.

AU - Neefjes, Jacques

AU - Schumacher, Ton N.

AU - Hutt-Fletcher, Lindsey M.

AU - Wiertz, Emmanuel J.H.J.

PY - 2003/9/30

Y1 - 2003/9/30

N2 - Epstein-Barr virus (EBV) persists lifelong in infected hosts despite the presence of antiviral immunity. Many viral antigens are expressed during lytic infection. Thus, for EBV to spread, it must have evolved effective ways to evade immune recognition. Here, we report that HLA class II-restricted antigen presentation to T helper cells is hampered in the presence of the lytic-phase protein gp42. This interference with T cell activation involves association of gp42 with class II peptide complexes. Using HLA-DR tetramers, we identify a block in T cell receptor (TCR)-class II interactions imposed by gp42 as the underlying mechanism. EBV gp42 sterically clashes with TCR Vα-domains as visualized by superimposing the crystal structures for gp42-HLA-DR1 and TCR-MHC class II complexes. Blocking TCR recognition provides a previously undescribed strategy for viral immune evasion.

AB - Epstein-Barr virus (EBV) persists lifelong in infected hosts despite the presence of antiviral immunity. Many viral antigens are expressed during lytic infection. Thus, for EBV to spread, it must have evolved effective ways to evade immune recognition. Here, we report that HLA class II-restricted antigen presentation to T helper cells is hampered in the presence of the lytic-phase protein gp42. This interference with T cell activation involves association of gp42 with class II peptide complexes. Using HLA-DR tetramers, we identify a block in T cell receptor (TCR)-class II interactions imposed by gp42 as the underlying mechanism. EBV gp42 sterically clashes with TCR Vα-domains as visualized by superimposing the crystal structures for gp42-HLA-DR1 and TCR-MHC class II complexes. Blocking TCR recognition provides a previously undescribed strategy for viral immune evasion.

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EP - 11588

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 20

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Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition

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