The Src-like adaptor protein downregulates the T cell receptor on CD4+CD8+ thymocytes and regulates positive selection.
In this report, we show that the Src-like adaptor protein (SLAP) plays an important role in thymocyte development. SLAP expression is developmentally regulated; it is low in CD4-CD8- thymocytes, it peaks in the CD4+CD8+ subset, and it decreases to low levels in more mature cells. Disruption of the SLAP gene leads to a marked upregulation of TCR and CD5 expression at the CD4+CD8+ stage. The absence of SLAP was also developmentally significant because it enhanced positive selection in mice expressing the DO11.10 transgenic T cell receptor. Moreover, SLAP deletion at least partially rescued the development of ZAP-70-deficient thymocytes. These results demonstrate that SLAP participates in a novel mechanism of TCR downregulation at the CD4+CD8+ stage and regulates positive selection.
Sosinowski
T
T
Departments of Microbiology and Immunology, University of California at San Francisco, San Francisco, CA 94143, USA.
Killeen
N
N
Weiss
A
A
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis*; D018956:CD5 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D037181:Lectins, C-Type; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D018956:CD5 Antigens; D016827:CD8 Antigens; D037181:Lectins, C-Type; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D011948:Receptors, Antigen, T-Cell; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099192:CD69 Antigens; C095148:Sla protein, mouse; C497262:Zap70 protein, mouse