Genomic mining of new genes and pathways in innate and adaptive immunity.
Plant disease resistant (R) genes constitute a large family that mediates host response to bacteria, viruses and fungi. Large mammalian proteins containing a nucleotide binding domain (NBD) and C-terminal leucine-rich repeats (LRRs) are similar in structure to the TLR/NBD/LRR subfamily of R proteins and have been suggested as a link between innate and acquired immunity. Because of our long-term interest in one of these, the class II transactivator (CIITA), and recent reports linking mutations in two new NBD/LRR proteins (Nod2/CARD 15 and CIAS 1/cryopyrin) to various autoimmune and inflammatory disorders, we have performed a comprehensive search of the human genome and found a multigene family which we termed the CATERPILLAR (CARD, Transcription Enhancer, R[purine]-binding, Pyrin, Lots of Leucine Regions)family. The N-termini of these genes are varied although the majority have a pyrin domain and few have a CARD domain. The genomic organization of these genes demonstrates a high degree of conservation with the NBD encoded as a single large exon and the LRRs encoded in two basic arrangements. Detailed analysis and new functional data regarding a number of the CATERPILLAR proteins will be described, including CIITA, cryopyrin and Monarch 1.
Department of Microbiology-Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jenny
J
Ting
D000222:Adaptation, Physiological / Q000235:genetics / Q000276:immunology; D016678:Genome; D007113:Immunity, Innate / Q000235:genetics*