Allelic exclusion of the T cell receptor beta 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-beta 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-alpha/beta transgene into the SLP-76(-/-) background fails to cause expansion of DN thymocytes or developmental progression to the DP stage. Moreover, analysis of TCR-beta 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-beta allelic exclusion.
Aifantis
I
I
Institut National de la Santé et Recherche Medicale (INSERM) U373, Hôpital Necker Enfants-Malades, Paris cedex 15, France.
Pivniouk
V I
VI
Gärtner
F
F
Feinberg
J
J
Swat
W
W
Alt
F W
FW
von Boehmer
H
H
Geha
R S
RS
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D051379:Mice; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018909:src Homology Domains / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D010750:Phosphoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C092947:SLP-76 signal Transducing adaptor proteins