Regulation of thymocyte development through CD3: functional dissociation between p56lck and CD3 sigma in early thymic selection.
We studied the extent of functional linkage between CD3 sigma and p56lck in pre-TCR-dependent thymocyte development. Differentiation of DN to DP cells was examined by treatment of RAG2/CD3 sigma and RAG1/p56lck double-deficient mice with anti-CD3 epsilon antibodies. The results suggest that CD3 sigma has no specific role in this maturation step, but may be important for amplification of signaling through the pre-TCR. In contrast, p56lck is the main protein tyrosine kinase associated with signaling through the pre-TCR-CD3 complex. In DP thymocytes, the Ca2+ response to anti-CD3 epsilon was totally abolished in CD3 sigma-I-but only reduced in p56lck-I-mice, and in vivo responses to anti-CD3 epsilon differed from one another. Thus, CD3 sigma and p56lck are functionally not tightly associated and their deficiencies cause distinct developmental defects.
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Max Planck Institut für Immunobiologie, Freiburg, Federal Republic of Germany.
Mombaerts
P
P
Wang
B
B
Kohler
H
H
Tonegawa
S
S
Eichmann
K
K
Terhorst
C
C
D000818:Animals; D001483:Base Sequence; D017252:CD3 Complex / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D018398:Homeodomain Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D017931:DNA Primers; D018398:Homeodomain Proteins; D011506:Proteins; D015375:Receptors, Interleukin-2; C064658:RAG-1 protein; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D002118:Calcium