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IMGT unique numbering for V-DOMAIN and V-LIKE-DOMAIN

Citing IMGT unique numbering for V-DOMAIN and V-LIKE-DOMAIN:
Lefranc, M.-P., Immunology Today, 18, 509 (1997) PMID: 9386342
Lefranc, M.-P., The Immunologist, 7, 132-136 (1999) pdf
Lefranc, M.-P. et al., Dev. Comp. Immunol., 27, 55-77 (2003) PMID: 12477501 pdf with permission from Elsevier

New 'IMGT Protein display for V domain' header: pdf doc

The V-DOMAIN corresponds to the V-J-REGION and V-D-J-REGION of the immunoglobulin (IG) and T cell receptor (TR) chains.
The V-LIKE-DOMAIN corresponds to a domain of similar structure as V-DOMAIN, found in chains other than IG or TR.

IMGT unique numbering for V-DOMAIN

The IMGT numbering for V-DOMAIN (IG and TR) is derived from the princeps of IMGT unique numbering for V-REGION [1]. Up to position 104, the IMGT unique numbering for V-DOMAIN follows that numbering.

The IMGT unique numbering has been defined to compare the variable domains whatever the antigen receptor, the chain type, or the species [1-3]. In the IMGT unique numbering, the conserved amino acids always have the same position, for instance cysteine 23 (1st-CYS), tryptophan 41 (CONSERVED-TRP), hydrophobic amino acid 89, cysteine 104 (2nd-CYS), phenylalanine or tryptophan 118 (J-PHE or J-TRP). The IMGT unique numbering provides a standardized delimitation of the framework regions (FR1-IMGT: positions 1 to 26, FR2-IMGT: 39 to 55, FR3-IMGT: 66 to 104 and FR4-IMGT: 118 to 128) and of the complementarity determining regions: CDR1-IMGT: 27 to 38, CDR2-IMGT: 56 to 65 and CDR3-IMGT: 105 to 117. As gaps represent unoccupied positions, the CDR-IMGT lengths (shown between brackets and separated by dots, e.g. [8.8.13]) become crucial information. The IMGT unique numbering is used in 2D graphical representations, designated as IMGT Colliers de Perles [4, 5], and in 3D structures in IMGT/3Dstructure-DB [6].

Gaps in the CDR1-IMGT and CDR2-IMGT (less than 12 and 10 amino acid long, respectively) are put at the top of the CDR-IMGT loops, as in IMGT/3Dstructure-DB (gaps shown as dashes, in the table below).

CDR1-IMGT
lengths		 CDR1-IMGT
27-38
(5-12)
12 27 28 29 30 31 32 33 34 35 36 37 38
11 27 28 29 30 31 32 - 34 35 36 37 38
10 27 28 29 30 31 - - 34 35 36 37 38
9 27 28 29 30 31 - - - 35 36 37 38
8 27 28 29 30 - - - - 35 36 37 38
7 27 28 29 30 - - - - - 36 37 38
6 27 28 29 - - - - - - 36 37 38
5 27 28 29 - - - - - - - 37 38
CDR2-IMGT
lengths		 CDR2-IMGT
56-65
(0-10)
10 56 57 58 59 60 61 62 63 64 65
9 56 57 58 59 60 - 62 63 64 65
8 56 57 58 59 - - 62 63 64 65
7 56 57 58 59 - - - 63 64 65
6 56 57 58 - - - - 63 64 65
5 56 57 58 - - - - - 64 65
4 56 57 - - - - - - 64 65
3 56 57 - - - - - - - 65
2 56 - - - - - - - - 65
1 56 - - - - - - - - -
0 - - - - - - - - - -

The basic length of a rearranged CDR3-IMGT is 13 amino acids (positions 105 to 117), which corresponds to a JUNCTION of 15 amino acids (2nd-CYS 104 to J-TRP or J-PHE 118).

This length and corresponding numbering were chosen since they are convenient to use. Indeed, 80% of the IG and TR rearranged sequences in IMGT/LIGM-DB have a CDR3-IMGT length less than or equal to 13 amino acids.

If the CDR3-IMGT length is less than 13 amino acids, gaps are created from the top of the loop, in the following order 111, 112, 110, 113, 109, 114, etc.

CDR3-IMGT
lengths		 Gaps for CDR3-IMGT lengths < 13 amino acids
13 105 106 107 108 109 110 111 112 113 114 115 116 117
12 105 106 107 108 109 110 - 112 113 114 115 116 117
11 105 106 107 108 109 110 - - 113 114 115 116 117
10 105 106 107 108 109 - - - 113 114 115 116 117
9 105 106 107 108 109 - - - - 114 115 116 117
8 105 106 107 108 - - - - - 114 115 116 117
7 105 106 107 108 - - - - - - 115 116 117
6 105 106 107 - - - - - - - 115 116 117
5 105 106 107 - - - - - - - - 116 117
---

If the CDR3-IMGT length is more than 13 amino acids, additional positions are created between positions 111 and 112 at the top of the CDR3-IMGT loop in the following order 112.1,111.1, 112.2, 111.2, 112.3, 111.3, etc.

CDR3-IMGT
lengths		 Additional positions between 111 and 112 for CDR3-IMGT lengths > 13 amino acids
---
21 111 111.1 111.2 111.3 111.4 112.4 112.3 112.2 112.1 112
20 111 111.1 111.2 111.3 - 112.4 112.3 112.2 112.1 112
19 111 111.1 111.2 111.3 - - 112.3 112.2 112.1 112
18 111 111.1 111.2 - - - 112.3 112.2 112.1 112
17 111 111.1 111.2 - - - - 112.2 112.1 112
16 111 111.1 - - - - - 112.2 112.1 112
15 111 111.1 - - - - - - 112.1 112
14 111 - - - - - - - 112.1 112

The IMGT unique numbering for V-DOMAIN is used in IMGT Colliers de Perles [2], IMGT Protein displays, and 3D representations of the V-J-REGION and V-D-J-REGION of the immunoglobulin and T cell receptor chains. The same rules are used for both the numbering of the CDR3-IMGT of V-DOMAIN and the numbering of the FG loop of C-DOMAIN. Indeed, we showed that the hydrogen bonds between 2nd-CYS 104 and position 119 in the C-DOMAIN correspond structurally to the hydrogen bonds between 2nd-CYS 104 and the Glycine which follows the J-TRP or J-PHE in the J-REGION (and therefore numbered as Glycine 119) [1]. The IMGT unique numbering for V-DOMAIN and the IMGT unique numbering for C-DOMAIN allow therefore, for the first time, to compare the length and the structure of the CDR3-IMGT of V-DOMAIN with the FG loop of C-DOMAIN.

IMGT unique numbering for V-LIKE-DOMAIN

The IMGT unique numbering for V-LIKE-DOMAIN (proteins other than IG or TR) follows exactly the same rules as those of the IMGT unique numbering for V-DOMAIN [1].

Positions 118 and 119 are identified by amino acid sequence alignment. Analysis of the 3D structure may be useful to identify position 119 which usually has hydrogen bonds to 2nd-CYS 104.

References:
[1] Lefranc M.-P., "Unique database numbering system for immunogenetic analysis" Immunology Today, 18, 509 (1997). PMID: 9386342
[2] Lefranc M.-P., "The IMGT unique numbering for Immunoglobulins, T cell receptors and Ig-like domains" The Immunologist, 7, 132-136 (1999). pdf
[3] Lefranc, M.-P., Pommié, C., Ruiz, M., Giudicelli, V., Foulquier, E., Truong, L., Thouvenin-Contet, V. and Lefranc, G., "IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains" Dev. Comp. Immunol., 27, 55-77 (2003). PMID: 12477501 pdf
[4] Ruiz, M. and Lefranc, M.-P. "IMGT gene identification and Colliers de Perles of human immunoglobulin with known 3D structures" Immunogenetics, 53, 857-883 (2002). PMID: 11862387
[5] Kaas, Q. and Lefranc, M.-P. "IMGT Colliers de Perles: standardized sequence-structure representations of the IgSF and MhcSF superfamily domains" Current Bioinformatics, 2, 21-30 (2007).
[6] Kaas, Q., Ruiz, M. and Lefranc, M.-P. "IMGT/3Dstructure-DB and IMGT/StructuralQuery, a database and a tool for immunoglobulin, T cell receptor and MHC structural data" Nucl. Acids. Res., 32, D208-D210 (2004). PMID: 14681396 pdf

Acknowledgements:
We thank Elsevier and Developmental and Comparative Immunology, for allowing IMGT to make available the DCI pdf file on the IMGT site.

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