Building an immune system from nine domains.
Four families of PRRs (pattern-recognition receptors) have been identified as important components of innate immunity, participating in the sensory system for host defence against the invasion of infectious agents. The TLRs (Toll-like receptors) recognize a variety of conserved microbial PAMPs (pathogen-associated molecular patterns) derived from bacteria, viruses, protozoa and fungi. They work in synergy with the cytosolic NLRs [NOD (nucleotide binding and oligomerization domain)-like receptors] (which sense bacteria), RLRs [RIG-I (retinoic acid-inducible gene 1)-like receptors] (which sense viruses) and CLRs (C-type lectin receptors) (which sense fungi). All of these receptor families signal an increase in the expression of a range of immune and inflammatory genes. The structural architecture of these receptors is conserved, involving seven distinct domains: the LRR (leucine-rich repeat) domain, the TIR [Toll/IL (interleukin)-1 receptor] domain, the NBS (nucleotide-binding site), the CARD (caspase recruitment domain), the PYD (pyrin domain), the helicase domain and the CTLD (C-type lectin domain). Two other domains, the Ig domain and the ITAM (immunoreceptor tyrosine-based activation motif) domain also participate and are also found in antibodies and TCRs (T-cell receptors), key proteins in adaptive immunity. This total of nine domains can therefore be used to construct immune systems which are common to many, if not all, species, allowing us to speculate on the minimum requirement for a complex immune system in structural terms. These insights are important for our overall understanding of the regulation of immunity in health and disease.
Pålsson-McDermott
E M
EM
School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. palssone@tcd.ie
O'Neill
L A J
LA
D001665:Binding Sites; D020169:Caspases / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007127:Immunoglobulin Constant Regions / Q000276:immunology; D053577:Interleukin-1 Receptor Accessory Protein / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D000090263:Leucine-Rich Repeat Proteins; D009711:Nucleotides / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000276:immunology; D000071198:Pyrin; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014443:Tyrosine / Q000276:immunology
D003598:Cytoskeletal Proteins; D007127:Immunoglobulin Constant Regions; D053577:Interleukin-1 Receptor Accessory Protein; D037181:Lectins, C-Type; D000090263:Leucine-Rich Repeat Proteins; C000604192:MEFV protein, human; D009711:Nucleotides; D011506:Proteins; D000071198:Pyrin; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D020169:Caspases