TCR down-regulation controls virus-specific CD8+ T cell responses.
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.
Bonefeld
Charlotte Menné
CM
Department of International Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Haks
Mariëlle
M
Nielsen
Bodil
B
von Essen
Marina
M
Boding
Lasse
L
Hansen
Ann Kathrine
AK
Larsen
Jeppe Madura
JM
Odum
Niels
N
Krimpenfort
Paul
P
Kruisbeek
Ada
A
Christensen
Jan Pravsgaard
JP
Thomsen
Allan Randrup
AR
Geisler
Carsten
C
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology; D000818:Animals; D001117:Arenaviridae Infections / Q000235:genetics / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000276:immunology; D010455:Peptides / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018116:Vesiculovirus / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D014764:Viral Proteins