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Contents

Complement

Chapter:
Nomenclature
Author(s):

Harriet S. Meyer

Complement

  • It is estimated that one C3b deposited on an organ-
  • ism can become four million in about 4 min.
  •  M. K. Liszewski and J. P. Atkinson14(p922)

The term complement refers to a group of serum proteins activated sequentially and rapidly in a cascade that produces molecules providing resistance to pathogens.14-16 The system was named in 1899 for its complementarity with antibodies in destroying microbes.15

Current nomenclature derives largely from the 1968 World Health Organization Bulletin “Nomenclature of Complement,”17 with subsequent modifications as mechanisms of action were further elucidated.

Three complement activation pathways are recognized: the classical pathway (activation by antibody), the alternative pathway (despite the name, the more phylogenetically ancient), and the lectin pathway. They culminate in a common terminal pathway. Components of the classical and terminal pathways are designated with a C and a number, reflective of the order of discovery of the component rather than the reaction sequence. (The prime, as in C′, has been discontinued.) Letters and abbreviations other than C typify the components of the other pathways. Complement component terms need not be expanded:

Pathway

Components

classical

C1, C4, C2

alternative

factors D, B, P (P for properdin [“destruction-bringing”14])

Lectin or MBLectin

mannose-binding lectin (MBL), MBL-associated serine protease 1 (MASP-1), MASP-2, MASP-3

terminal

C5, C6, C7, C8, C9

C3 (common to all pathways)

Fragments.

Appended lowercase letters indicate complement fragments. Usually, a lowercase b indicates the larger, active (membrane-binding) fragment and a lowercase a, the smaller, release fragment (released on cleavage of the parent molecule). However, C2 is inconsistent: C2a is the larger active fragment and C2b the smaller release fragment. Other letters represent fragments of b fragments.

C3a

C3b

C3c

C3d

Cdg

C3f

C4a

C4b

C4c

C4d

C5a

C5b

Bb

Subunits.

The subunits of C1 are as follows:

C1q

C1r

C1s

Various notations combining the C1 subunits convey the stoichiometry (relative quantities of subunits) of the complex; all such styles are acceptable:

(C1r)2

C1r2C1s2

C1qC1r2C1s2

C1qr2s2

C1s-C1r-C1r-C1s

Isotypes of C4 have capital letters appended:

C4A

C4B

Protein chains have Greek letters appended:

C8α

C8β

C8γ

C3α is the α chain of C3.

Cleavage of C3α produces C3a and C3b.

An i signifies inactive forms:

iC3 or C3i

iC3b

Complement components that form a complex are written in a series without spaces:

C4b2a3b

C4bC2

Sometimes a hyphen is used to indicate a series:

C5b67 or C5b-7

C5-9

An asterisk shows nascent or metastable state:

C4b*

C3b*

C5b*

C5b-7*

Convertase complexes are linked complement fragments that activate other complement components. For example, the convertase that activates C3 is known as C3 convertase. As in the following examples, the convertases have different compositions, depending on which complement pathway generated them:

Classical Pathway

Alternative Pathway

C3 convertase

C4b2a

C3bBb

C3bBbP

C3(H2O)Bb(Mg2+)

C5 convertase

C4b2a3b

C3bBbC3b

(C3b)2Bb

(Note: Occasionally, authors have changed the designation of the activated moiety of C2 from C2a to C2b, to be consistent with other complement components.18,19(p8) A tipoff to the change is the designation of classical pathway C3 convertase as C4b2b.)

A bar over the suffix was proposed in 1968 to designate activated complement, eg: Complement but this convention has fallen from use.

Complement Regulators.

Complement regulators include the following:

Name

Other Terms

C1 inhibitor (C1-INH)

C1 esterase inhibitor, C1 esterase INH

C3 membrane proteinases

C4 binding protein (C4bp)

carboxypeptidases

CD59

membrane inhibitor of reactive lysis (MIRL), membrane attack complex-inhibitory factor (MACIF), homologous restriction factor 20 (HRF20), P18, protectin

decorin

delay accelerating factor (DAF)

CD55

factor H

formerly β1H

factor I [letter I, not roman numeral “one”]

factor H-like protein (FHL-1)

membrane cofactor protein (MCP)

CD46

S protein*

vitronectin

SP-40,40

clusterin

(*Not the same as protein S; see 15.7.4, Hemostasis, Inhibition of Coagulation and Fibrinolysis.)

Complement Receptors.

Complement receptors include the following:

Name

Other Terms

complement receptor type 1 (CR1)

C3b receptor, CD35

CR2

C3d receptor, CD21, CD21S (short isoform), CD21L (long isoform)

CR3

Mac-1, CD11b/CD18

CR4

p150/95, CD11c/CD18

C3Ar

C4Ar

C5Ar

CD88

cC1Qr

collectin receptor; c prefix: collagen region of C1q

gC1Qr

g prefix: globular head portion of C1q

C1qRp

factor H receptor (fH-R)

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