The essential role of LAT in thymocyte development during transition from the double-positive to single-positive stage.
The linker for activation of T cells (LAT) is an adaptor protein that couples TCR engagement to downstream signaling cascades. LAT is important in early thymocyte development as LAT-deficient mice have a complete block at the double-negative (DN) 3 stage. To study the role of LAT beyond the DN3 stage, we generated mice in which the lat gene could be deleted by the Cre recombinase. Analysis of these mice showed that deletion of LAT after the DN3 stage allowed thymocytes to develop past the DN3 to DN4 checkpoint and to generate double-positive thymocytes. However, LAT-deficient DP thymocytes were severely defective in responding to stimulation via the TCR and failed to differentiate into single-positive thymocytes efficiently. Consequently, few LAT-deficient mature T cells could be found in the periphery. These T cells had undergone extensive homeostatic proliferation and expressed low levels of the TCR on their surface. Collectively, our data indicate that in addition to its role in pre-TCR signaling, LAT also plays an essential role in thymocyte development during transition from the double-positive to single-positive stage.
Shen
Shudan
S
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Zhu
Minghua
M
Lau
Jasmine
J
Chuck
Mariana
M
Zhang
Weiguo
W
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D016827:CD8 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D055879:Gene Knock-In Techniques; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015704:CD4 Antigens; D016827:CD8 Antigens; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D011948:Receptors, Antigen, T-Cell