Antibody Information

The Kabat Numbering Scheme

The Kabat numbering scheme is a widely adopted standard for numbering the residues in an antibody in a consistent manner. However the scheme has problems!

First, since the numbering scheme was developed from sequence data (a fairly limited set), the position at which insertions occur in CDR-L1 and CDR-H1 does not match the structural insertion position. Thus topologically equivalent residues in these loops do not get the same number.

Second, the numbering adopts a rigid specification. For example in the potentially very long CDR-H3, insertions are numbered between residue H100 and H101 with letters up to K (i.e. H100, H100A ... H100K, H101). If there are more residues than that, there is no standard way of numbering them. Such situations occur at other positions too.

The numbering throughout the chains is as follows:

Light chain

          0     1     2     3     4     5     6     7     8     9
          10    11    12    13    14    15    16    17    18    19
          20    21    22    23    24    25    26    27
          27A   27B   27C   27D   27E   27F               28    29
          30    31    32    33    34    35    36    37    38    39
          40    41    42    43    44    45    46    47    48    49
          50    51    52    53    54    55    56    57    58    59
          60    61    62    63    64    65    66    67    68    69
          70    71    72    73    74    75    76    77    78    79
          80    81    82    83    84    85    86    87    88    89
          90    91    92    93    94    95
          95A   95B   95C   95D   95E   95F   96    97    98    99
          100   101   102   103   104   105   106
          106A                                      107   108   109
        

Heavy chain

          0     1     2     3     4     5     6     7     8     9
          10    11    12    13    14    15    16    17    18    19
          20    21    22    23    24    25    26    27    28    29
          30    31    32    33    34    35
          35A  35B                            36    37    38    39
          40    41    42    43    44    45    46    47    48    49
          50    51    52
          52A   52B   52C   53    54    55    56    57    58    59
          60    61    62    63    64    65    66    67    68    69
          70    71    72    73    74    75    76    77    78    79
          80    81    82
          82A   82B   82C   83    84    85    86    87    88    89
          90    91    92    93    94    95    96    97    98    99
          100
          100A  100B  100C  100D  100E  100F  100G  100H  100I  100J
          100K  101   102   103   104   105   106   107   108   109
          110   111   112   113
        

The Chothia Numbering Scheme

The Chothia numbering scheme is identical to the Kabat scheme, 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).

There are two disadvantages: first, the Kabat scheme is so widely used that some confusion can arise; second, Chothia et al. changed their numbering scheme as of their 1989 Nature paper such that insertions in CDR-L1 are placed after residue L31 rather than L30. Examining the conformations of the loops shows that L30 is the correct position.

Note That in their latest paper (Al-Lazikani et al., (1997) JMB 273,927-948), Chothia's group returns to using residue L30 as the insertion site in CDR-L1!

The pre-1989/post-1997 Chothia numbering (the structurally correct version) throughout the chains follows.

Light chain

          0     1     2     3     4     5     6     7     8     9
          10    11    12    13    14    15    16    17    18    19
          20    21    22    23    24    25    26    27    28    29
          30    
          30A   30B   30C   30D   30E   30F
          31    32    33    34    35    36    37    38    39
          40    41    42    43    44    45    46    47    48    49
          50    51    52    53    54    55    56    57    58    59
          60    61    62    63    64    65    66    67    68    69
          70    71    72    73    74    75    76    77    78    79
          80    81    82    83    84    85    86    87    88    89
          90    91    92    93    94    95
          95A   95B   95C   95D   95E   95F   96    97    98    99
          100   101   102   103   104   105   106
          106A                                      107   108   109
        

Heavy chain

          0     1     2     3     4     5     6     7     8     9
          10    11    12    13    14    15    16    17    18    19
          20    21    22    23    24    25    26    27    28    29
          30    31    
          31A   31B
          32    33    34    35    36    37    38    39
          40    41    42    43    44    45    46    47    48    49
          50    51    52
          52A   52B   52C   53    54    55    56    57    58    59
          60    61    62    63    64    65    66    67    68    69
          70    71    72    73    74    75    76    77    78    79
          80    81    82
          82A   82B   82C   83    84    85    86    87    88    89
          90    91    92    93    94    95    96    97    98    99
          100
          100A  100B  100C  100D  100E  100F  100G  100H  100I  100J
          100K  101   102   103   104   105   106   107   108   109
          110   111   112   113
        

Martin (Enhanced Chothia) Numbering Scheme

The only differences between the Chothia and Kabat numbering schemes are in the sites of indels in CDR-L1 and CDR-H1.

Our 'Martin' (Enhanced Chothia) scheme also considers the structurally correct locations for indels in the framework regions. Thus the numbering scheme is identical to the Chothia in most regards but positions of framework indels have been refined.

The most important of these is the insertion which present in the majority of antibodies at H82a,b,c has been moved to the structurally correct location of H72a,b,c.

We have also introduced an indel site at L52 in CDR-L2. All structures have the standard length of 7 residues and the conformations are relatively conserved. However sequences of varying length are seen and analysis of the structure suggests this is the correct location. It also corresponds with the AHo numbering scheme.

In this scheme, the locations of deleted residues are indicated with ().

A manuscript describing this new scheme is in preparation.

Light chain

          0     1     2     3     4     5     6     7     8     9 
          (10)   11    12    13    14    15    16    17    18    19 
          20    21    22    23    24    25    26    27    28    29
          (30)
          30A   30B   30C   30D   30E   30F
          31    32    33    34    35    36    37    38    39
          40
          40A  (41)   42    43    44    45    46    47    48    49 
          50    51    (52)    
          52A   52B   52C   52D   52E   
          53    54    55    56    57    58    59
          60    61    62    63    64    65    66    67   (68)
          68A   68B   68C   68D   68E   68F   68G   68H         69
          70    71    72    73    74    75    76    77    78    79
          80    81    82    83    84    85    86    87    88    89
          90    91    92    93    94   (95)
          95A   95B   95C   95D   95E   95F   96    97    98    99
          100   101   102   103   104   105   106   107
          107A                                            108   109
          110
        

Heavy chain

          0     1     2     3     4     5     6     7    (8)
          8A    8B    8C    8D                                  9
          10    11    12    13    14    15    16    17    18    19
          20    21    22    23    24    25    26    27    28    29
          30   (31)
          31A   31B
          32    33    34    35    36    37    38    39
          40    41   (42)   43    44    45    46    47    48    49 
          50    51   (52)
          52A   52B   52C   53    54    55    56    57    58    59
          60    61    62    63    64    65    66    67    68    69
          70    71    72
          72A   72B   72C   73    74    75    76    77    78    79
          80    81    82    83    84    85    86    87    88    89
          90    91    92    93    94    95    96    97    98    99
          (100)
          100A  100B  100C  100D  100E  100F  100G  100H  100I  100J
          100K  101   102   103   104   105   106   107   108   109
          110   111   112   113
        

Table of CDR Definitions

A number of definitions of the CDRs are commonly in use:

  • The Kabat definition is based on sequence variability and is the most commonly used
  • The Chothia definition is based on the location of the structural loop regions
  • The AbM definition is a compromise between the two used by Oxford Molecular's AbM antibody modelling software
  • The contact definition has been recently introduced by us and is based on an analysis of the available complex crystal structures. This definition is likely to be the most useful for people wishing to perform mutagenesis to modify the afinity of an antibody since these are residues which take part in interactions with antigen. Lists of CDR residues making contact in each antibody with summary data for each CDR
LoopKabat AbM Chothia1 Contact2 IMGT
L1 L24--L34 L24--L34 L24--L34 L30--L36 L27--L32
L2 L50--L56 L50--L56 L50--L56 L46--L55 L50--L51
L3 L89--L97 L89--L97 L89--L97 L89--L96 L89--L97
H1 H31--H35B
(Kabat Numbering)3
H26--H35BH26--H32..34H30--H35BH26--H35B
H1 H31--H35
(Chothia Numbering)
H26--H35 H26--H32 H30--H35 H26--H33
H2 H50--H65 H50--H58 H52--H56 H47--H58 H51--H56
H3 H95--H102 H95--H102H95--H102 H93--H101H93--H102

Note (1) some of these definitions (particularly for Chothia loops) vary depending on the individual publication examined.

Note (2) any of the numbering schemes can be used for these CDR defintions, except the contact definition uses the Chothia or Martin (Enhanced Chothia) definition.

Note (3) the end of the Chothia CDR-H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop. (This is because the Kabat numbering scheme places the insertions at H35A and H35B.)

  • If neither H35A nor H35B is present, the loop ends at H32
  • If only H35A is present, the loop ends at H33
  • If both H35A and H35B are present, the loop ends at H34
H1 Definition

This diagram illustrates the alternative definitions for CDR-H1. The Kabat and Chothia numbering schemes are shown horizontally and the Kabat, Chothia, AbM and Contact definitions of the CDRs are shown with arrows above and below the two numbering schemes.


How to identify the CDRs by looking at a sequence

The following set of rules will allow you to find the CDRs in an antibody sequence. Note that the word 'always' should always be treated with care! There are rare examples where these virtually constant features do not occur (for example the human heavy chain sequence EU does not have Trp-Gly after CDR-H3). The Cys residues are the best conserved feature.

CDR-L1

Start
Approx residue 24
Residue before 
always a Cys
Residue after
always a Trp. Typically Trp-Tyr-Gln, but also, Trp-Leu-Gln, Trp-Phe-Gln, Trp-Tyr-Leu
Length
10 to 17 residues

CDR-L2

Start
always 16 residues after the end of L1
Residues before 
generally Ile-Tyr, but also, Val-Tyr, Ile-Lys, Ile-Phe
Length
always 7 residues (except NEW (7FAB) which has a deletion in this region)

CDR-L3

Start
always 33 residues after end of L2 (except NEW (7FAB) which has the deletion at the end of CDR-L2)
Residue before 
always Cys
Residues after
always Phe-Gly-XXX-Gly
Length
7 to 11 residues

CDR-H1

Start
Approx residue 26 (always 4 after a Cys) [Chothia / AbM defintion];
Kabat definition starts 5 residues later
Residues before 
always Cys-XXX-XXX-XXX
Residues after
always a Trp. Typically Trp-Val, but also, Trp-Ile, Trp-Ala
Length
10 to 12 residues [AbM definition];
Chothia definition excludes the last 4 residues

CDR-H2

Start
always 15 residues after the end of Kabat / AbM definition) of CDR-H1
Residues before 
typically Leu-Glu-Trp-Ile-Gly, but a number of variations
Residues after
Lys/Arg-Leu/Ile/Val/Phe/Thr/Ala-Thr/Ser/Ile/Ala
Length
Kabat definition 16 to 19 residues;
AbM (and recent Chothia) definition ends 7 residues earlier

CDR-H3

Start
always 33 residues after end of CDR-H2 (always 2 after a Cys)
Residues before 
always Cys-XXX-XXX (typically Cys-Ala-Arg)
Residues after
always Trp-Gly-XXX-Gly
Length
3 to 25(!) residues

Table of mean contact data

Following an analysis of the contacts between antibody and antigen in the complex structures available in the Protein Databank, we have generated a set of mean contact data. The full method by which these results were obtained is described in the following paper: MacCallum, R. M., Martin, A. C. R. and Thornton, J. T. 'Antibody-antigen interactions: Contact analysis and binding site topography' J. Mol. Biol. 262:732-745.

Briefly, we analysed the number of contacts made at each position, defining contact as burial by > 1 square Angstrom change in solvent accessibility. These data give a simple measure of how likely a residue is to be involved in antigen contact.

Second, we calculated the mean percentage burial over the accessible residues.

The 'Mean Contacts' table presents the chain name, residue number (pre-1989 Chothia Numbering), the number of contacts and the mean percent burial.

An 'Simplified View' is a list of CDR residues making contact in each antibody with summary data for each CDR.

Mean Contacts Simplified View

Composite combining site containing all CDR conformations from 1986 coloured by contact propensity.