Antibody Numbering Schemes¹¶

IMGT¶

IMGT²³ has 128 possible positions for all antigen receptor types (IG and TR). These are supposed to be structurally equivalent. In theory these are supposed to account for all possible positions, with an insertion point only between positions 111 and 112 in the CDR3 for lengths exceeding 13 amino acids, e.g. 111-ABCD DCBA-112.

As the length of the CDR regions increases, the IMGT numbering of the added residues does not increment in a naive way. E.g., for HCDR1 of length 5 the numbering is "27 28 29 37 38", then for each added residue, the numbering follows the pattern "36 30 35 31 34 32 33" rather than "30 31 32 33 34 35 36". Thus, for HCDR1 of length 6, the numbering is "27 28 29 36 37 38 39".

When filling the gap within the minimal CDR numberings (see table below), larger numbers takes precedence over smaller numbers (e.g. 36 before 30, 112A before 111A).

Region	Length range	Minimal numbering	New numberings as length increases
CDR1	5-12	27 28 29 -- 37 38	36 30 35 31 34 32 33
CDR2	0-10	--	56 65 57 64 58 63 59 62 60 61
CDR3	5-91	105 106 107 -- 116 117	115 108 114 109 113 110 112 111 112A 111A 112B 111B ...

Kabat¶

Kabat⁴ is defined for heavy and light antibody chains only. Positions in the two chain types are not equivalent. Maximum number is 113 for heavy and 109 for light. Insertions occur at specific positions and can occur in both the framework and the CDRs. They are annotated from A->Z. e.g 100ABCDEFGHIJK 101.

Region	Numbering	Possible insertion codes
[H]CDR1	35	ABCD
[H]CDR2	52	ABC
[H]FR3	82	ABC
[H]CDR3	100	ABCDEFGHIJK
[L]CDR1	27	ABCDEF
[L]CDR3	95	ABCDEF
[L]FR4	106	A

Despite its global popularity, the Kabat scheme is now known to have limitations:

Undefined for very long HCDR3s: In the potentially very long HCDR3, insertions are numbered between residue H100 and H101 with letters up to K (i.e. 100ABCDEFGHIJK 101). We now know it is possible to have more residues than that, but there is no defined way of numbering them.
Structurally uninformed: The Kabat numbering scheme was developed from a limited sequence dataset, without the knowledge of structure. We now know that the position at which insertions occur in LCDR1 and HCDR1 does not actually match the structural insertion position. Thus topologically equivalent residues in these loops do not get the same number.

Chothia¶

Chothia⁵⁶⁷ is defined for heavy and light antibody chains only. Numbering in the two chain types are not equivalent. Maximum number is 113 for heavy and 109 for light (same as Kabat). Insertions occur at specific positions and can occur in both the framework and the CDRs. They are annotated from A->Z. e.g 100ABCDEFGH 101.

The Chothia numbering scheme is based on Kabat, but places the insertions in CDR-L1 and CDR-H1 at the structurally correct positions. This means that topologically equivalent residues in these loops do get the same label (unlike the Kabat scheme).

Region	Numbering	Possible insertion codes
[H]CDR1	31	AB
[H]CDR2	52	ABC
[H]FR3	82	ABC
[H]CDR3	100	ABCDEFGHIJK
[L]CDR1	30	ABCDEF
[L]CDR3	95	ABCDEF
[L]FR4	106	A

AHo¶

AHo has 149 possible for all antigen receptor types (IG and TR). These are supposed to be structurally equivalent. The AHo scheme's large number of positions is supposed to account for all possible positions without the need for specifying insertion positions.

Similar to IMGT, insertions and deletions in the AHo numbering are placed symmetrically around key positions, rather than growing from one direction. For example, the gap in immunoglobulin CDR2s is centered around position 63, resulting in an 8-residue gap in the VL domains (L59-L66, placed between L50 and L51 according to Kabat) and a 1-to-4-residue gap in VH domains (between H52 and H53 according to Kabat). For more details, please refer to the AHo official website.

AHo 1-33 is aligned to IMGT 1-33, AHo 36-119 is aligned to IMGT 34-117, AHo 139-149 to IMGT 118-128.

CDR definition comparison¶

Note that these numbers include residues with insertion codes, for example, Kabat HCDR1 (31-35) include residues 31-34 35ABCD.

Scheme	HCDR1	HCDR2	HCDR3	LCDR1	LCDR2	LCDR3
IMGT	27-38	56-65	105-117	27-38	56-65	105-117
IMGT (Chothia-numbered)	26-35	51-57	93-102	27-32	50-52	89-97
Kabat	31-35	50-65	95-102	24-34	50-56	89-97
Chothia	26-32	52-56	96-101	26-32	50-52	91-96
North (Chothia-numbered)	23-35	50-58	93-102	24-34	49-56	89-97

You may find more detailed comparison between the CDR numbering of IMGT and Kabat/Chothia scheme of VH, VK, VL genes on the IMGT website. Here is an example with some real-world sequences.

Conserved sequences around CDRs¶

The following set of rules will allow you to locate the CDR region in an antibody sequence through the neighboring conserved residues.

Region	IMGT	Kabat/Chothia	Amino acids
Before HCDR1	23	22	C
After HCDR1	41-42	36-37	WV, WI, WA
Before HCDR2	50-54	45-49	LEWIG
After HCDR2	75-77	66-68	K/R - L/I/V/F/T/A - T/S/I/A
Before HCDR3	104-106	92-94	CAR, CXX
After HCDR3	118-121	103-106	WGXG
Before LCDR1	23	23	C
After LCDR1	41-43	35-37	WYQ, WLQ, WFQ, WYL
Before LCDR2	54-55	48-49	IY, VY, IK, IF
After LCDR2
Before LCDR3	104	88	C
After LCDR3	118-121	98-101	FGXG

The bold residues are conserved under most cases, while the italic residues are less frequent.

Vernier Zone¶

Vernier zone residues⁹ are located in the framework regions and underlie the complementary determining regions (CDRs). These residues potentially affect the conformation of CDR loop structures, thus are frequently back-mutated during CDR grafting to prevent affinity loss.

Region	Kabat/Chothia	IMGT
Before HCDR1	H2,27-30	H2,28-31
Before HCDR2	H47-49	H52-54
After HCDR2	H67,69,71,73	H76,78,80,82
Before HCDR3	H93-94	H105-106
After HCDR3	H103-104	H118-119
Before LCDR1	L2,L4	L2,L4
After LCDR1	L35-36	L41-42
Before LCDR2	L46-49	L52-55
After LCDR2	L64,66,67,69,71	L78,80,84,85,87
After LCDR3	L98	L118

This document is adapted from the ANARCI documentation and documentation by Prof. Andrew Martin's Group ↩
IMGT unique numbering for V-REGION: Lefranc, M.-P. et al., Dev. Comp. Immunol., 27, 55-77 (2003) PubMed pdf ↩
IMGT unique numbering for V-DOMAIN and V-LIKE-DOMAIN: Lefranc, M.-P. et al., Dev. Comp. Immunol., 27, 55-77 (2003) PubMed pdf ↩
Kabat, E.A. et al., In: Sequences of Proteins of Immunological Interest, NIH Publication, 91-3242 (1991). ↩
Chothia, C. and Lesk, A.M., J. Mol. Biol., 196, 901-917 (1987). ↩
Chothia, C. et al., Nature, 342, 877-883 (1989). ↩
Al-Lazikani, B. et al., J. Mol. Biol., 273, 927-948 (1997). ↩
A. Honegger & A. Plückthun. J. Mol. Biol, 309 (2001)657-670. PubMed pdf ↩
Jefferson Foote; Greg Winter, J. Mol. Biol. 224, 487-499 (1992). ↩

Antibody Numbering Schemes1¶