Somatic hypermutations by insertion or deletion in rearranged cDNA: Human IGHV

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

Antibody name
Antibody specificity
Rearranged IGH V-D-J-REGIONs
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.
#c: Rearranged cDNA.
 

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
Accession
numbers
 CDR-IMGT length (2)
IGHV
gene and allele name
Accession
numbers
CDR-IMGT
length

ST
(IgG)
[6]

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*01M99660 [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.
#c: Rearranged cDNA.

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: Friday, 27-May-2016 21:03:40 CEST
Author: Johanne Abad

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