Abstract
The signaling lymphocytic activation molecule (SLAM) family of receptors are expressed on the majority of immune cells. These receptors often serve as self-ligands, and play important roles in cellular communication and adhesion, thus modulating immune responses. SLAM family receptor signaling is differentially regulated in various immune cell types, with responses generally being determined by the presence or absence of two SLAM family adaptor proteins—Ewing’s sarcoma-associated transcript 2 (EAT-2) and SLAM-associated adaptor protein (SAP). In addition to serving as direct regulators of the immune system, certain SLAM family members have also been identified as direct targets for specific microbes and viruses. Here, we will discuss the known roles for these receptors in the setting of viral infection, with special emphasis placed on HIV infection. Because HIV causes such complex dysregulation of the immune system, studies of the roles for SLAM family receptors in this context are particularly exciting.
Highlights
The signaling lymphocytic activation molecule (SLAM) family of receptors are expressed on the majority of immune cells
We have shown previously that altering SLAM family signaling by overexpressing Ewing’s sarcoma-associated transcript 2 (EAT-2) enhanced both innate and adaptive immune responses to antigens such as HIV-Gag [22]
We found that SLAMF7 signaling in human monocytes inhibits the production of various alpha chemokines, but not host restriction factors that are critical for combatting HIV-1 infection at the cellular level
Summary
The signaling lymphocytic activation molecule (SLAM) family of receptors are a set of nine conserved cell-surface glycoproteins present on the cell surface of immune cells (Table 1). XLP is characterized by alterations of cellular and humoral immune responses, predisposing young males to Epstein–Barr virus (EBV)-associated morbidity and mortality The discovery of this genetic association spurred research into the function of SAP, its ligands—the SLAM family of receptors—and what role these molecules play in immune regulation and response to infection. Efforts to distill the basic elements of this system have revealed that, in general, SLAM family receptors can have activating or inhibitory functions on immune cells Whether or not they function to promote immune cell activation typically depends on the presence of their adaptors, SAP and/or EAT-2. In the presence of these adaptors, ligation of SLAM family receptors often results in cellular activation, and in their absence, vice-versa [2] This simple regulatory mechanism is most conserved and apparent in SLAMF7 and SLAMF4 regulated networks. For more detailed information on the specifics of SLAM family receptor signaling and the various adaptors capable of binding SLAM family members, please refer to any of these reviews [1,2,4,5]
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