Channel catfish leukocyte immune-type receptor mediated inhibition of cellular cytotoxicity is facilitated by SHP-1-dependent and -independent mechanisms

Induction of Phagocytosis and Intracellular Signaling by an Inhibitory Channel Catfish Leukocyte Immune-Type Receptor: Evidence for Immunoregulatory Receptor Functional Plasticity in Teleosts

“…Alternatively, inhibitory IpLITR types abrogated NK cell-mediated killing via SHP-dependent and SHP-independent mechanisms [31,34], which was revealed after transfection and expression of these proteins in primary mouse NK cells. Since catfish myeloid cells also express inhibitory IpLITR types, we examined the signaling and functional potential of an inhibitory IpLITR type in RBL-2H3 cells and compared its activities to that of a previously characterized stimulatory IpLITR [33].…”

“…To date, IpLITR ligands have not been discovered and this has hindered our ability to understand their specific roles in teleost immunity. However, by expressing these receptors in representative mammalian myeloid and lymphoid cell types, important insights into IpLITR signaling capabilities and control of immune cell effector responses have been revealed [31,32,33,34]. Although heterologous overexpression of fish immune proteins in mammalian cells has potential drawbacks, in the absence of monoclonal antibodies (mAb) and reliable transfection procedures for expression in fish cells, this approach has provided important new information regarding the immunoregulatory potential of these teleost proteins.…”

A Leukocyte Immune-Type Receptor Subset Is a Marker of Antiviral Cytotoxic Cells in Channel Catfish, Ictalurus punctatus

“…Alternatively, CC41 mAb may prevent target recognition (conjugate formation) altogether, by blocking the interaction between multiple LITRs isoforms and their ligands, regardless of their signaling capability. Nevertheless, this observed inhibition of cytotoxicity, together with the activating and inhibitory signaling potentials of LITRs (35)(36)(37)(38) and their phylogenetic relationships with FCRL and LILR/KIR receptors (31, 32) argues for LITRs having direct roles in target cell recognition and/or subsequent signal transduction.…”

“…As for inhibitory receptors, constructs containing the extracellular portion of human NK receptor KIRDL3 fused with the CYT of TS32.17 LITR1.2a or TS32.17 LITR1.1b transiently expressed in HEK 293T cells recruited epitope tagged zebrafish Src homology 2 domain-containing protein tyrosine phosphatases SHP-1 and SHP-2 (35). Also, when the same receptors were expressed in mouse spleen-derived cytotoxic cells, killing of MHC class Ideficient targets was significantly inhibited (36). More recently, it was demonstrated that the inhibitory TS32.17 LITR 1.1b, which in addition to two ITIMs contains an atypical ITAM-like (ExxYx 2 Vx 16 Yx 2 V) sequence and an ITSM in its CYT, also mediated phagocytosis when expressed in rat basophilic leukemia-2H3 cells (39).…”

“…Catfish inhibitory LITRs have a neutral transmembrane (TM) and a cytoplasmic tail (CYT) containing one or more ITIMs, whereas activating forms have a charged lysine residue in their TM allowing for association with signaling adaptors and a short CYT. In addition, there are some LITRs with long CYT that contain an atypical ITAM-like sequence, two ITIMs, and a immunoreceptor tyrosinebased switch motif (ITSM) (31,32,(35)(36)(37)(38)(39).…”