Mining of channel catfish (Ictalurus punctatus) expressed sequence tag databases identified seven new novel immune type receptors (IpNITRs). These differed in sequence, but not structure, from previously described IpNITR1-11. IpNITR12a, 12b, 13, and 14 encode proteins containing a single variable (V)-like immunoglobulin (Ig) domain. IpNITR12a and 13 encode a transmembrane (TM) region and cytoplasmic tail (CYT) containing immunoreceptor tyrosine inhibition motifs (ITIMs). IpNITR14 contains a TM and short CYT devoid of signaling motifs and is similar in structure to IpNITR7. IpNITR12b lacks a TM and may represent an IpNITR12a splice variant. In contrast, IpNITR15a, 15b, and 16 encode two Ig domains (V-like domain 1 and V/C2-like domain 2). IpNITR15a and 15b contain TM and CYT with ITIMs. IpNITR16 appears to be a secreted form. The first V-like domains of IpNITR12-16 (except a/b pairs) share 17-32% amino acid identity with each other and with V domains of IpNITR1-11. They therefore represent five additional IpNITR V families (defined as possessing 70% or more amino acid identity). The V/C2 domains of IpNITR15a, 15b and 16 have 94-98% amino acid identity, but share 37-50% amino acid identity with corresponding V/C2 domains found in IpNITR1-4. Phylogenetic analyses indicate IpNITR12-16 are more closely related to other teleost NITRs than to IpNITR1-11. Gene mapping indicates that IpNITRs are linked, and members of the ten known IpNITR families are interspersed. IpNITR12-16 are differentially expressed in various catfish immune-type cells and preferentially up regulated in peripheral blood leukocytes by allogeneic stimulation.