Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein

Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4(−)CD8(−) double-negative (DN) thymocytes into CD4(+)CD8(+) double-positive (DP) cells and for TCR-β allelic exclusion. The adaptor protein SH2 domain–containing leukocyte protein (SLP)-76 ha...

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Autores principales: Aifantis, Iannis, Pivniouk, Vadim I., Gärtner, Frank, Feinberg, Jacqueline, Swat, Wojciech, Alt, Frederick W., von Boehmer, Harald, Geha, Raif S.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195661/
https://www.ncbi.nlm.nih.gov/pubmed/10523607
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author Aifantis, Iannis
Pivniouk, Vadim I.
Gärtner, Frank
Feinberg, Jacqueline
Swat, Wojciech
Alt, Frederick W.
von Boehmer, Harald
Geha, Raif S.
author_facet Aifantis, Iannis
Pivniouk, Vadim I.
Gärtner, Frank
Feinberg, Jacqueline
Swat, Wojciech
Alt, Frederick W.
von Boehmer, Harald
Geha, Raif S.
author_sort Aifantis, Iannis
collection PubMed
description Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4(−)CD8(−) double-negative (DN) thymocytes into CD4(+)CD8(+) double-positive (DP) cells and for TCR-β allelic exclusion. The adaptor protein SH2 domain–containing leukocyte protein (SLP)-76 has been shown to play a crucial role in thymic development, because thymocytes of SLP-76(−/−) mice are arrested at the CD25(+)CD44(−) DN stage. Here we show that SLP-76(−/−) DN thymocytes express the pre-TCR on their surfaces and that introduction of a TCR-α/β transgene into the SLP-76(−/−) background fails to cause expansion of DN thymocytes or developmental progression to the DP stage. Moreover, analysis of TCR-β rearrangement in SLP-76(−/−) TCR-transgenic mice or in single CD25(+)CD44(−) DN cells from SLP-76(−/−) mice indicates an essential role of SLP-76 in TCR-β allelic exclusion.
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spelling pubmed-21956612008-04-16 Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein Aifantis, Iannis Pivniouk, Vadim I. Gärtner, Frank Feinberg, Jacqueline Swat, Wojciech Alt, Frederick W. von Boehmer, Harald Geha, Raif S. J Exp Med Original Article Signaling via the pre-T cell receptor (TCR) is required for the proliferative expansion and maturation of CD4(−)CD8(−) double-negative (DN) thymocytes into CD4(+)CD8(+) double-positive (DP) cells and for TCR-β allelic exclusion. The adaptor protein SH2 domain–containing leukocyte protein (SLP)-76 has been shown to play a crucial role in thymic development, because thymocytes of SLP-76(−/−) mice are arrested at the CD25(+)CD44(−) DN stage. Here we show that SLP-76(−/−) DN thymocytes express the pre-TCR on their surfaces and that introduction of a TCR-α/β transgene into the SLP-76(−/−) background fails to cause expansion of DN thymocytes or developmental progression to the DP stage. Moreover, analysis of TCR-β rearrangement in SLP-76(−/−) TCR-transgenic mice or in single CD25(+)CD44(−) DN cells from SLP-76(−/−) mice indicates an essential role of SLP-76 in TCR-β allelic exclusion. The Rockefeller University Press 1999-10-18 /pmc/articles/PMC2195661/ /pubmed/10523607 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Aifantis, Iannis
Pivniouk, Vadim I.
Gärtner, Frank
Feinberg, Jacqueline
Swat, Wojciech
Alt, Frederick W.
von Boehmer, Harald
Geha, Raif S.
Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
title Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
title_full Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
title_fullStr Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
title_full_unstemmed Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
title_short Allelic Exclusion of the T Cell Receptor β Locus Requires the Sh2 Domain–Containing Leukocyte Protein (Slp)-76 Adaptor Protein
title_sort allelic exclusion of the t cell receptor β locus requires the sh2 domain–containing leukocyte protein (slp)-76 adaptor protein
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195661/
https://www.ncbi.nlm.nih.gov/pubmed/10523607
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