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IG interchain disulfide bridges per monomer

Citing this table: Lefranc, M.-P. and Lefranc, G., The Immunoglobulin FactsBook, Academic Press, London, UK (458 pages), 2001, ISBN:012441351X

1. Structural and biological properties of human immunoglobulins

2. Human immunoglobulin (IG) chain characteristics

4. Lysines and cysteines of the Homo sapiens IGHG1, IGKC and IGLC1 and positions in the C-DOMAIN

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

6. IMGT engineered variant nomenclature: IGHG variants

7. Homo sapiens IGHG1 amino acids involved in the interactions with the C1q, FcγR and FCGRT

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:
17/01/2019
Authors:
Souphatta Sasorith and Marie-Paule Lefranc
Editor:
Chantal Ginestoux