Regulatory role of leukocyte-common-antigen-related molecule (LAR) in thymocyte differentiation.
The strength of interaction between the antigenic peptide-loaded MHC (MHC/p) and the TCR determines T-cell fate in the thymus. A high avidity interaction between the TCR and the MHC/p induces apoptosis of self-reactive T cells (negative selection), whereas a moderate avidity interaction rescues thymocytes from apoptosis and permits further differentiation to mature T cells (positive selection). Leukocyte common antigen-related molecule (LAR), a receptor-like protein tyrosine phosphatase, is expressed on immature thymocytes, but its role in thymocyte differentiation has not yet been fully elucidated. We analyzed LAR-deficient mice and demonstrated that LAR deficiency affected the differentiation and expansion of immature thymocytes as well as positive and negative selection. Furthermore, LAR deficiency resulted in a lower Ca2+ response. The results indicate that LAR is an important modulator of TCR signaling that controls thymocyte differentiation.
Kondo
Sachiko
S
Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan.
Kishi
Hiroyuki
H
Muraguchi
Atsushi
A
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017637:Clonal Deletion / Q000502:physiology; D005260:Female; D038041:Lymphopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology*
D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2