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 Odum; Paul Krimpenfort; Ada Kruisbeek; Jan Pravsgaard Christensen; Allan Randrup Thomsen; Carsten Geisler

doi:10.4049/jimmunol.181.11.7786

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 Odum, Paul Krimpenfort, Ada Kruisbeek, Jan Pravsgaard Christensen, Allan Randrup Thomsen, Carsten Geisler

Sundhed og Teknologi - Institut for Teknologiske Uddannelser

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma 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 CD3gamma di-leucine-based motif. The CD3gamma 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 CD3gamma-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)	7786-99
Number of pages	14
ISSN	0022-1767
DOIs	https://doi.org/10.4049/jimmunol.181.11.7786
Publication status	Published - 1 Dec 2008

Keywords

Amino Acid Motifs
Animals
Antigens, CD3
Arenaviridae Infections
CD8-Positive T-Lymphocytes
Down-Regulation
Lymphocytic choriomeningitis virus
Mice
Mice, Transgenic
Mutation
Peptides
Proto-Oncogene Proteins c-bcl-2
Receptors, Antigen, T-Cell
Rhabdoviridae Infections
Signal Transduction
Vesiculovirus
Viral Proteins

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10.4049/jimmunol.181.11.7786

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

abstract = "The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma 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 CD3gamma di-leucine-based motif. The CD3gamma 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 CD3gamma-mediated TCR down-regulation in virus-specific CD8(+) T cell responses.",

keywords = "Amino Acid Motifs, Animals, Antigens, CD3, Arenaviridae Infections, CD8-Positive T-Lymphocytes, Down-Regulation, Lymphocytic choriomeningitis virus, Mice, Mice, Transgenic, Mutation, Peptides, Proto-Oncogene Proteins c-bcl-2, Receptors, Antigen, T-Cell, Rhabdoviridae Infections, Signal Transduction, Vesiculovirus, Viral Proteins",

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 Odum and Paul Krimpenfort and Ada Kruisbeek and Christensen, {Jan Pravsgaard} and Thomsen, {Allan Randrup} and Carsten Geisler",

year = "2008",

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doi = "10.4049/jimmunol.181.11.7786",

language = "English",

volume = "181",

pages = "7786--99",

journal = "Journal of Immunology",

issn = "0022-1767",

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TY - JOUR

T1 - TCR down-regulation controls virus-specific CD8+ T cell responses

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 - Odum, Niels

AU - Krimpenfort, Paul

AU - Kruisbeek, Ada

AU - Christensen, Jan Pravsgaard

AU - Thomsen, Allan Randrup

AU - Geisler, Carsten

PY - 2008/12/1

Y1 - 2008/12/1

N2 - The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma 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 CD3gamma di-leucine-based motif. The CD3gamma 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 CD3gamma-mediated TCR down-regulation in virus-specific CD8(+) T cell responses.

AB - The CD3gamma di-leucine-based motif plays a central role in TCR down-regulation. However, little is understood about the role of the CD3gamma 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 CD3gamma di-leucine-based motif. The CD3gamma 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 CD3gamma-mediated TCR down-regulation in virus-specific CD8(+) T cell responses.

KW - Amino Acid Motifs

KW - Animals

KW - Antigens, CD3

KW - Arenaviridae Infections

KW - CD8-Positive T-Lymphocytes

KW - Down-Regulation

KW - Lymphocytic choriomeningitis virus

KW - Mice

KW - Mice, Transgenic

KW - Mutation

KW - Peptides

KW - Proto-Oncogene Proteins c-bcl-2

KW - Receptors, Antigen, T-Cell

KW - Rhabdoviridae Infections

KW - Signal Transduction

KW - Vesiculovirus

KW - Viral Proteins

U2 - 10.4049/jimmunol.181.11.7786

DO - 10.4049/jimmunol.181.11.7786

M3 - Journal article

C2 - 19017968

SN - 0022-1767

VL - 181

SP - 7786

EP - 7799

JO - Journal of Immunology

JF - Journal of Immunology

IS - 11

ER -

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

Abstract

Keywords

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