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IG interchain disulfide bridges per monomer




Structural and biological properties of human immunoglobulins

Human immunoglobulin (IG) chain characteristics

Amino acid positions involved in ADCC, CDC, half life and half-IG exchange

Human (Homo sapiens) IG classes

Disulfide bridges Chain Classes and subclasses
IgM IgD IgG IgA IgE
IgG1 IgG2 IgG3 IgG4 IgA1 IgA2
Inter H-L H (1) Number 1 1 1 1 1 1 1 1 1?
Positions CH1: 10 CH1: 11 h 5 CH1: 10 CH1: 10 CH1: 10 CH1: 10 CH1: 123 CH1: 10, 11
L (2) C-KAPPA 126 (last residue)
C-LAMBDA 126 (last-but-one residue)
Inter H-H H (1) Number 1 1 2 4 11 2 2? 2? 1?
Positions CH2: 125 CH2: 1.6 h 11, h 14 h 4, h 5, h 8, h 11 H1: h 13, h 16
H2: h 5, h 11, h 14
H3: h 5, h 11, h 14
H4: h 5, h 11, h 14
h 8, h 11 CH2: 1.1, 1.2 CH2: 1.1, 1.2 CH2: 1.6, 11, 124

In INN, cysteines of the hinge involved in inter-chain bridges are indicated with a small letter 'h', for example, for an Homo sapiens IgG1 - kappa: Inter-H-L (h 5-CL 126), Inter-H-H (h 11, h 14).


Mouse (Mus musculus) IG classes

Disulfide bridges Chain Classes and subclasses
IgM IgD IgG IgA IgE
IgG1 IgG2A IgG2B IgG2C IgG3
Inter H-L H (1) Number 1 1 1 1 1 1 1 1? 1
Positions CH1: 10 CH1: 10 h 5 CH1: 11 CH1: 11 CH1: 11 CH1: 11 CH1: 123
CH2: 1.1
CH1: 10
L (2) C-KAPPA 126 (last residue)
C-LAMBDA 126 (last-but-one residue)
Putative inter H-H H (1) Number 1 0 3 3 4 3 1 ? 2
Positions CH2: 125 no H-H bridge h 7, h 10, h 12 h 10, h 13, h 15 h 12, h 15, h 18, h 21 h 11, h 17, h 20 h 15 ? CH2: 11, 124

In INN, cysteines of the hinge involved in inter-chain bridges are indicated with a small letter 'h', for example, for a Mus musculus IgG2B - kappa: Inter-H-L (CH1 11-CL 126), Inter-H-H (h 12, h 15, h 18, h 21).


Human (Homo sapiens) IgG2 disulfide isoforms

Three isoforms of the Homo sapiens IgG2 have been identified which differ by their inter-chain disulfide bridges [1, 2, 3].

The isoform A is classically characterized by:
- two inter H-L (CH1 10-CL126) (one for each Fab arm)
- four inter-H (h 4, h 5, h 8, h 11) disulfide bridges

In the isoform A/B, one of the two inter-H-L (CH1 10-CL 126) on one Fab arm and the inter-H-H (h 4 - h 4) are replaced by an inter-H-H (h 4 - CH1 10) and an inter-H-L (h 4 - CL 126).

The isoform B is characterized by an additional change, the inter-H-L (CH1 10 - CL 126) on the second Fab arm and the inter-H-H (h 5 - h 5) being replaced by an an inter-H-H (h 5 - CH1 10) and an inter-H-L (h 5 - CL 126).

The isoform A is predominant for IgG2-lambda, the isoform A/B is equally represented for both IgG2-kappa and IgG2-lambda, whereas in contrast the isoform B is only found for IgG2-kappa, not for IgG2-lambda [1, 2]. As CL 126 is terminal for C-KAPPA and subterminal for C-LAMBDA, it has been proposed that the presence of the serine in 127 of the lambda chain may sterically interferes with the formation of the disulfide bridge [2].


Disulfide bridges of the Homo sapiens IgG2 disulfide isoforms

Isoform A Isoform A/B Isoform B
Inter-H-L (CH1 10 - CL 126) Inter-H-L (CH1 10 - CL 126) Inter-H-L (h 5 - CL 126)
Inter-H-L (CH1 10 - CL 126) Inter-H-L (h 4 - CL 126) Inter-H-L (h 4 - CL 126)
Inter-H-H (h 4 - h 4) Inter-H-H (h 4 - CH1 10) Inter-H-H (h 4 - CH1 10)
Inter-H-H (h 5 - h 5) Inter-H-H (h 5 - h 5) Inter-H-H (h 5 - CH1 10)
Inter-H-H (h 8 - h 8) Inter-H-H (h 8 - h 8) Inter-H-H (h 8 - h 8)
Inter-H-H (h 11 - h 11) Inter-H-H (h 11 - h 11) Inter-H-H (h 11 - h 11)

It is not excluded that other disulfide bridges may occur between the same cysteines.



Schematic representation of the IgG2 disulfide isoforms

Isoform A Isoform A/B Isoform B
IgG2  XX representation


Notes:
(1) H: heavy chain
(2) L: light chain (kappa or lambda)

See also:


IMGT references:
  1. [1] Wypych J. et al J Biol Chem 283, 16194-16205 (2008). PMID: 18339624
  2. [2] Dillon T.M. et al. J Biol Chem 283,16206-16215 (2008). PMID: 18339626
  3. [3] Liu Y.D. et al J Biol Chem 283, 29266-29272 (2008). PMID: 18713741
Created:
11/12/2012
Last updated:
27/05/2016
Authors:
Souphatta Sasorith and Marie-Paule Lefranc
Editor:
Chantal Ginestoux