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.