TCR down-regulation controls virus-specific CD8+ T cell responses

Charlotte Menné Bonefeld; Mariëlle Haks; Bodil Nielsen; Marina Von Essen; Lasse Boding; Ann Kathrine Hansen; Jeppe Madura Larsen; Niels Ødum; Paul Krimpenfort; Ada Kruisbeek; Jan Pravsgaard Christensen; Allan Randrup Thomsen; Carsten Geisler

TCR down-regulation controls virus-specific CD8⁺ T cell responses

Charlotte Menné Bonefeld, Mariëlle Haks, Bodil Nielsen, Marina Von Essen, Lasse Boding, Ann Kathrine Hansen, Jeppe Madura Larsen, Niels Ødum, Paul Krimpenfort, Ada Kruisbeek, Jan Pravsgaard Christensen, Allan Randrup Thomsen, Carsten Geisler^*

^*Corresponding author for this work

14 Citations (Scopus)

Abstract

The CD3γ di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3γ di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8⁺ T cells is impaired in mice with a mutated CD3γ di-leucine-based motif. The CD3γ mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8⁺ T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3γ-mediated TCR down-regulation in virus-specific CD8⁺ T cell responses.

Original language	English
Journal	Journal of Immunology
Volume	181
Issue number	11
Pages (from-to)	7786-7799
Number of pages	14
ISSN	0022-1767
Publication status	Published - 1 Dec 2009

Cite this

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title = "TCR down-regulation controls virus-specific CD8+ T cell responses",

abstract = "The CD3γ di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3γ di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8+ T cells is impaired in mice with a mutated CD3γ di-leucine-based motif. The CD3γ mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8+ T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3γ-mediated TCR down-regulation in virus-specific CD8+ T cell responses.",

author = "Bonefeld, {Charlotte Menn{\'e}} and Mari{\"e}lle Haks and Bodil Nielsen and {Von Essen}, Marina and Lasse Boding and Hansen, {Ann Kathrine} and Larsen, {Jeppe Madura} and Niels {\O}dum and Paul Krimpenfort and Ada Kruisbeek and Christensen, {Jan Pravsgaard} and Thomsen, {Allan Randrup} and Carsten Geisler",

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AU - Bonefeld, Charlotte Menné

AU - Haks, Mariëlle

AU - Nielsen, Bodil

AU - Von Essen, Marina

AU - Boding, Lasse

AU - Hansen, Ann Kathrine

AU - Larsen, Jeppe Madura

AU - Ødum, Niels

AU - Krimpenfort, Paul

AU - Kruisbeek, Ada

AU - Christensen, Jan Pravsgaard

AU - Thomsen, Allan Randrup

AU - Geisler, Carsten

PY - 2009/12/1

Y1 - 2009/12/1

N2 - The CD3γ di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3γ di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8+ T cells is impaired in mice with a mutated CD3γ di-leucine-based motif. The CD3γ mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8+ T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3γ-mediated TCR down-regulation in virus-specific CD8+ T cell responses.

AB - The CD3γ di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3γ di-leucine-based motif in physiological T cell responses. In this study, we show that the expansion in numbers of virus-specific CD8+ T cells is impaired in mice with a mutated CD3γ di-leucine-based motif. The CD3γ mutation did not impair early TCR signaling, nor did it compromise recruitment or proliferation of virus-specific T cells, but it increased the apoptosis rate of the activated T cells by increasing down-regulation of the antiapoptotic molecule Bcl-2. This resulted in a 2-fold reduction in the clonal expansion of virus-specific CD8+ T cells during the acute phase of vesicular stomatitis virus and lymphocytic choriomeningitis virus infections. These results identify an important role of CD3γ-mediated TCR down-regulation in virus-specific CD8+ T cell responses.

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SN - 0022-1767

VL - 181

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EP - 7799

JO - Journal of Immunology

JF - Journal of Immunology

IS - 11

ER -

TCR down-regulation controls virus-specific CD8⁺ T cell responses

Abstract

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