Somatic hypermutations usually occur by transitions or transversions. However, a few examples of rearranged IGHV genes have been described in which somatic hypermutations correspond to insertions or deletions in the CDR-IMGT, or exceptionally in the FR-IMGT. These examples are reported and analysed in this table.
1/ Rearranged IGH V-D-J-REGIONs with defined specificity
IMGT reference sequence of the corresponding germline V-REGIONs (2) | Description of mutations by deletions/insertions
compared to the germline V-REGIONs |
|||||||
Accession numbers |
CDR-IMGT length (1) | IGHV gene and allele name | Accession numbers | CDR-IMGT length | ||||
ITC33 (IgG1) [1] [7] |
CMV gB Cytomegalovirus glycoprotein B |
L26531 | [11.8.14] #c | 5-51*01 | M99686 | [8.8.2] | 78^79>ins^gcagacggt 26^27>ins^ADG |
The 3 additional amino acids A (Ala), D (Asp) and G (Gly) are localised at the beginning of the CDR1-IMGT loop. Their position numbers are 26A, 26B and 26C, respectively. |
71-31 [7] |
HIV-1 p 24 | M67502 | [8.7.12] #c | 1-46*01 (3) | X92343 | [8.8.2] | a184-c186>del(3nt) S62>del(1AA) |
The deleted amino acid S62 corresponds to a position at the end of the CDR2-IMGT loop. |
K14 (IgG1, k) [4] [7] |
HIV-1 gp 41 | [8.9.13] #c | 3-23*01 | M99660 | [8.8.2] | 168^169>ins^att 56^57>ins^I | The additional codon att encoding isoleucine at position 56A is a duplication of codon 56 (att). The additional Ileu is localised at the beginning of the CDR2-IMGT loop. | |
HBp2 (IgM) [2] [7] |
Bordetella pertussis
lipooligosaccharide |
L21957 | [11.9.10] #c | 6-1*01 | X92224/ J04097 | [10.9.2] | 96^97>ins^agc 32^33>ins^S |
The additional codon agc encoding serine at position 32A is a duplication of codon 32 (agc). The additional Ser is localised at the top of the CDR1-IMGT loop. |
2/ Rearranged IGH V-D-J-REGIONs with unknown specificity
Antibody name | Rearranged IGH V-D-J-REGIONs | IMGT reference sequence of the corresponding germline V-REGIONs (2) | Description of the mutations by deletions/insertions compared to the germline V-REGIONs | ||||
numbers |
CDR-IMGT length (2) |
gene and allele name |
numbers |
length | |||
ST |
X94075 | [8.11.14] #c | 5-a*03 | X56375 | [8.8.2] | 177^178>ins^gatcctaat
59^60>ins^DPN |
The 3 additional amino acids D (Asp), P (Pro), N (Asn) are localised at the tip of the CDR2-IMGT loop. Their position numbers are 59A, 59B and 59C, respectively. |
BF2P2-g3C01 [3] |
Z80499 | [8.9.12] #c | 3-23*01 | M99660 | [8.8.2] | 168^169>ins^acc 56^57>ins^T |
The additional amino acid T (Thr) is localised at the beginning of the CDR2-IMGT loop. Its position number is 56A. |
3D15VH3 [3] |
X73172 | [8.X.X] #c | 3-23*01 | M99660 | [8.8.2] | g123-a172>del(50nt)# W41-S57>del(17AA)# |
The deletion of 50 nucleotides leads to a frameshift and encompasses the FR2-IMGT and the CDR2-IMGT. |
tm121 (IgM) [8] |
AF013615 | [10.9.X] #c | 6-1*01 | X92224/J04097 | [10.9.2] | 255^256>ins^aagaac 85^86>ins^KN |
The 2 additional amino acids K (Lys) and N (Asn) are localised in the middle of the FR3-IMGT. Their position numbers are 85A and 85B, respectively. |
[8] | AF013616 | [16.7.19] #c | 4-31*03 (4) | Z14237 | [10.7.2] | 87^88>ins^ttcacctctggtgactcc 29^30>ins^FTSGDS |
The 6 additional amino acids F (Phe), T(Thr), S (Ser), G (Gly), D (Asp) and S (Ser) are localised at the beginning of the CDR1-IMGT loop. Their corresponding numbers are 29A, 29B, 29C, 29D, 29E and 29F, respectively. |
[8] | AF013617 | [6.7.19] | 4-34*01 | X92278 | [8.7.2] | t97-c102>del(6nt,tactac)
Y33-Y34>del(2AA) |
The deleted amino acids Y33 and Y34 correspond to positions at the end of the CDR1-IMGT loop. |
[8] | AF013619 | [11.7.16] #c | 4-39*01 | L10094 | [10.7.2] | 102^103>ins^wac
34^35>ins^N/Y w: a or t wac: N (Asn) or Y (Tyr) |
The additional amino acid is localised at the end of the CDR1-IMGT loop. Its position number is 34A. |
IMGT notes:
(1) | The CDR-IMGT length modified by the insertion or the deletion is shown in red. |
(2) | Assignments to IGHV gene and alleles have been obtained by running IMGT/V-QUEST, with sequences from which inserted nucleotides have been omitted, or deleted nucleotides replaced by x. |
(3) | An identical score is obtained with 1-46*02 (J00240) and 1-46*03 (L06612). |
(4) | An identical score is obtained with 4-31*04 (M95120). |
References:
[1] | Andris, J.S. et al., Proc. Natl. Acad. Sci. U.S.A., 88, 7783-7787 (1991). |
[2] | Andris, J.S. et al., Mol. Immunol., 30, 1601-1616 (1993). |
[3] | Küppers, R. et al., EMBO J., 12, 4955-4967 (1993). |
[4] | Van der Donk, E.M.M. et al., AIDS Res. Human Retroviruses, 10, 1639-1649 (1994). |
[5] | Brezinschek, H.P. et al., J. Clin. Invest., 99, 2488-2501(1997). |
[6] | Snow, R.E. et al., Eur. J. Immunol., 27, 162-170 (1997). |
[7] | Ohlin, M and Borrebaeck, C.A.K., Mol. Immunol. 35, 233-238 (1998). |
[8] | Wilson, P.C. et al., J. Exp. Med., 187, 59-70 (1998). |
Created: 02/11/1999
Last updated: Wednesday, 31-Jul-2024 17:53:34 CEST
Author: Johanne Abad