Citing this page:
Lefranc, M.-P. et al., Dev. Comp. Immunol., 27, 55-77 (2003).
PMID: 12477501
FR-IMGT lengths
Lengths of the FR-IMGT from human V-DOMAIN are according to the
IMGT unique numbering for V-DOMAIN [1].
IMGT AA criteria for evaluation of immunogenecity
The lengths of the FR-IMGT are used for the IMGT evaluation of the immunogenicity of humanized variable domains [2].
Thus, the IMGT criteria include:
- the V-REGION identity percentage (%), by comparison with the closest human germline V gene and allele
(results form IMGT/DomainGapAlign),
- the number of different amino acids (AA) between the FR-IMGT of humanized antibodies and the FR-IMGT
of the closest human germline counterpart. If expressed as a ratio, the numerator is the number of different AA
and the denominator is the total length of the 4 FR-IMGT (91 AA for human VH, 89 for human V-KAPPA).
Number of different AA in FR/total FR-IMGT length
Humanized antibodies |
VH |
V-KAPPA |
alemtuzumab |
14/91 |
2/89 |
bevacizumab |
23/91 |
7/89 |
trastuzumab |
9/91 |
6/89 |
According to the IMGT® rules and IMGT Collier de Perles the number of different AA (or the numerator if expressed as a ratio)
should be zero, or at least as close as possible of zero [2].
- the number of AA class changes.
If expressed as a ratio, the numerator is the number of AA class changes and the denominator is the total length of the FR-IMGT
(IMGT classes of the 20 common amino acids for the
'hydropathy', 'volume', 'chemical characteristics' properties) [3].
|
Number of AA class changes in FR/total FR-IMGT length |
|
VH |
V-KAPPA |
alemtuzumab |
11/91 |
2/89 |
trastuzumab |
9/91 |
5/89 |
- the characterization of AA class changes. The AA class changes [3] are shown in the order:
hydropathy, volume and chemical characteristics, with a sign + (plus) if there is no class change and a sign - (minus)
if there is a class change, the 3 signs being shown between parentheses.
The comparison of two AA is defined by 5 categories. Two AA are:
- identical
- very similar (no class change): (+ + +), for example K>R
- similar (1 class change): (+ - +) (+ + -), for example I>V (+ - +), E>Q (+ + -)
- dissimilar (2 class changes): (+ - -), (- + -), (- - +), for example W>M (+ - -), Y>F (- + -), R>H (- - +)
- very dissimilar (3 class changes): (- - -), for example S>N (- - -).
Trastuzumab
VH
V-KAPPA
For VH and V-KAPPA, the IMGT Colliers de Perles on 2 layers and the 3D structure representations are from 1n8z_H (
IMGT/3Dstructure-DB).
3D structure representations are based on the IMGT Collier de Perles delimitations. The FR-IMGT, made of the 9 strands (arrows) and turns are in green, whereas the 3 CDR-IMGT are in red, orange and purple, respectively.
For amino acid changes with the closest germline V and J genes, see IMGT/DomainGapAlign results of VH 1n8z_H in
IMGT/3Dstructure-DB.
IMGT notes:
(1) |
Lengths for IGLV5 and IGLV11 subgroups. |
IMGT references:
[1] |
Lefranc, M.-P. et al., Dev. Comp. Immunol., 27, 55-77 (2003).
PMID: 12477501
with permission from Elsevier
|
[2] |
Magdelaine-Beuzelin, C. et al.,
Crit. Rev. Oncol. Hematol., 64, 210-225 (2007)
PMID: 17624800
|
[3] |
Pommié, C. et al.,
J. Mol. Recognit., 17, 17-32 (2004).
PMID: 14872534
|