In 2009 the International Complement Society (ICS) and the European Complement Network (ECN) began a joint reevaluation of the nomenclature for the complement system. Effective communication of scientific results requires terminology that is as simple, as clear and as unambiguous as possible. The last review was published in 1981 and much has changed since then. Complement is now known to be initiated by three independent pathways - the classical, alternative and lectin pathways - and many new proteins and receptors have been discovered.
In 1963, it was agreed that the components of complement were to be designated by the letter "C", the prime symbol, and numbers with activated products designated by the letter "a" added to the symbols (as in C1a for activated C1 and C2a for activated C2). At the time known components consisted of only nine proteins C'1, C'2, C'3, C'4, C'5, C'6 and C'7 with C'1 known to be a complex between C'1q, C'1r and C'1s.
By 1981 an entirely new pathway had been characterized and new proteins and complexes had been described. A subcommittee of the Nomenclature Committee of the International Union of Immunological Societies formalized the nomenclature for this "alternative" pathway of complement activation. Rather than continue numbering the components beyond C9 it was agreed that the components of this new pathway would be designated by letter symbols except for the C3 protein which was shared with the original activation pathway. The originally described pathway has since been referred to as the "classical" pathway of complement activation. Thus, constituents of the alternative pathway were designated factors B, D, H, I and P plus C3 and enzymatically active complexes were given designations such as C3b,Bb and C3b,Bb,C3b,P.
With the discovery of the lectin pathway and the characterization of many cellular receptors for complement activation fragments an entirely new set of components are now known to be involved in the activation of and the biological responses to complement. As is characteristic of any discovery process the nomenclature used for these new components is not uniform and is often redundant. Thus, the committee was charged with conducting the first formal evaluation of complement nomenclature since 1981.
|C1-INH||C1 Inhibitor (C1 esterase inhibitor)|
|C3(H2O)||Thioester-hydrolyzed form of C3|
|C3a||Anaphylatoxin from C3|
|C3a-desArg||C3a without C-terminal Arginine|
|C4a-desArg||C4a without C-terminal Arginine|
|C4BP||C4b binding protein|
|C5a||Anaphylatoxin from C5|
|C5a-desArg||C5a without C-terminal Arginine|
|Vn||Vitronectin (S protein, S40)|
|MBL||Mannose binding lectin|
|MASP-1||MBL-associated serine protease 1|
|MASP-2||MBL-associated serine protease 2|
|MASP-3||MBL-associated serine protease 3|
|FHL-1||Factor H-like protein 1|
|FHR-1||Factor H-related protein 1|
|FHR-2||Factor H-related protein 2|
|FHR-3||Factor H-related protein 3|
|FHR-4||Factor H-related protein 4|
|FHR-5||Factor H-related protein 5|
|CD59||Protectin, Homologous restriction factor|
|Cn||Clusterin (Apolipoprotein J, SP-40,40)|
|C5b6||Terminal pathway complex of C5b + C6|
|C5b-7||Terminal pathway complex of C5b6 + C7|
|C5b-8||Terminal pathway complex of C5b-7 + C8|
|C5b-9||Terminal pathway complete complex|
|sC5b-9||Soluble C5b-9 with Vn or Cn bound|
|C3bBb||Alternative pathway C3 convertase|
|C3bBbP||Alternative pathway C3 convertase with Properdin|
|C3bBbC3b||AP C3/C5 convertase|
|C4BP-Protein S||C4BP bound to Protein S|
|CR1||CD35 (C3b/C4b Receptor)|
|CR2||CD21 (C3d Receptor)|
|C3aR||Requesting CD number|
|C5aR2||(C5L2) Requesting CD number|
|CRIg||Complement receptor of the Ig family|
|gC1qR||Recognizes globular C1q domains|
|cC1qR||Calreticulin, Recognizes collagen domain|
|LHR||Long homologous repeat [in CR1]|
1. Kemper C, et al. (2014). Complement nomenclature 2014. Molecular immunology, 61(2), 56-58.
2. Alper C A, et al. (1981). Nomenclature of the alternative activating pathway of complement. J. Immunol. 127, 1261-1262.
3. Austen K F, et al. (1968). Nomenclature of complement. Bull. World Health Organ. 39, 935-938.
4. Karlson P, et al. (1981). Enzyme nomenclature. Recommendations 1978, Suppl.2, corrections and addition. Eur. J. Biochem. 116, 423-435.
5. Rapp H J, et al. (1963). Complement and hemolysis. Science 141, 738–740.