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The engagement of the antigen-receptor is essential for the activation of T or B lymphocytes. The signals following this event have been extensively characterized over the last two decades. Triggering the antigen-receptor is not the only factor in mediating lymphocyte activation. Multiple other receptor ligand interactions are necessary for a productive activation of naïve lymphocytes. These interactions can deliver co-stimulatory or inhibitory signals and are important for the fine-tuning of an immune response. The investigation of these modulating signals is the new challenge for understanding lymphocyte regulation. Natural killer cells do not possess a clonotypic antigen-receptor. They rely only on multiple receptor-ligand interactions causing positive or negative signals to regulate their activity. NK cells are therefore the ideal study object to investigate the important signals that modulate lymphocyte activation.

The recently discovered group of SLAM-related receptors (SRR) belongs to the CD2-family of Ig-like receptors and comprises six family members. While several members of the SRR were first discovered in NK cells, their expression can be found on many immune cells. Interestingly, several SRR family members serve as their own ligands through homophilic interactions. Engagement of SRR can modulate the activity of different immune cells, demonstrating that this receptor family is engaged in the fine-tuning of immune responses. The importance of this function is underscored by severe immune disorders caused by the disruption of SRR function. Recent data indicate that a polymorphism in the SRR gene cluster is associated with the susceptibility to systemic lupus erythematosus in mice. Another example are patients suffering from XLP (X-linked lymphoproliferative syndrome), a primary immunodeficiency that was first characterized by an inappropriate immune response to Epstein-Barr virus (EBV). XLP patients carry a mutation in a gene encoding for SAP (SH2D1A), an adaptor molecule that is important for the signal transduction of almost all SRR.


Figure1. The SLAM-related receptor family and their ligands.

Depicted are the six members of the SLAM-related receptor family with their cytoplasmic tails containing the ITSM signaling domains. On the opposing cell the corresponding ligands are shown.



Figure2. Signal transduction of the 2B4 receptor in NK cells.

(A) Early signaling events in 2B4-mediated NK cell activation. (B) Possible mechanism for 2B4-mediated NK cell inhibition in the absence of functional SAP e.g. in XLP patients.


In this project we will study the signal transduction and function of SRR during the interaction of different immune cells to learn more about the role of this receptor family during a successful immune reaction.


For further information please see:




Prof. Dr. Carsten Watzl

Institut für Immunologie

Ruprecht-Karls-Universität Heidelberg

Im Neuenheimer Feld 305

D-69120 Heidelberg, Germany

e-mail: watzl@uni-hd.de