“Stereotyped” amino acid changes
| Sequences . | Change . | CLL subset, n/N . | CLL heterogeneous, n/N . | Non-CLL, n/N . |
|---|---|---|---|---|
| IGHV1-2*02 sequences: IMGT-HFR2, codon 55 | W to R | Subset 1: 6/15 | 0/30 | 17/119 |
| IGHV1-2*02 sequences: IMGT-HFR2, codon 55 | W to R | Subset 28: 4/4 | 0/30 | 17/119 |
| IGHV3-21 sequences | Subset 2 | |||
| IMGT-HCDR1, codon 32 | S to T* | 11/56 | 6/29 | 12/95 |
| IMGT-HCDR1, codon 34 | S to N* | 9/56 | 2/29 | 7/95 |
| IMGT-HCDR2, codon 61 | S deletion | 18/56 | 0/29 | 1/95 |
| IMGT-HFR3, codon 66 | Y to H | 7/56 | 2/29 | 3/95 |
| IGHV4-34 sequences | Subset 4 | |||
| IMGT-HCDR1, codon 28 | G to D | 5/20 | 0/108 | 6/320 |
| IMGT-HCDR1, codon 28 | G to E | 8/20 | 6/108 | 18/320 |
| IMGT-HCDR1, codon 32 | G to D* | 7/20 | 20/108 | 49/320 |
| IMGT-HFR2, codon 40 | S to T | 10/20 | 29/108 | 45/320 |
| IMGT-HFR2, codon 45 | P to S | 10/20 | 17/108 | 33/320 |
| IGHV4-34 sequences | Subset 16 | |||
| IMGT-HCDR1, codon 28 | G to E | 6/7 | 6/108 | 18/320 |
| IMGT-HFR2, codon 40 | S to T | 4/7 | 29/108 | 45/320 |
| IMGT-HFR2, codon 45 | P to S | 3/7 | 17/108 | 33/320 |
| IGHV4-4 sequences | Subset 14 | |||
| IMGT-HCDR1, codon 33 | S to N | 3/4 | 0/17 | 8/90 |
| IMGT-HFR2, codon 40 | S to T | 4/4 | 4/17 | 12/90 |
| IMGT-HCDR2, codon 57 | Y to H | 4/4 | 3/17 | 7/90 |
| IMGT-HCDR2, codon 58 | H to P | 3/4 | 0/17 | 0/90 |
| IMGT-HFR3, codon 78 | I to M | 4/4 | 6/17 | 8/90 |
| IMGT-HFR3, codon 92 | S to N | 3/4 | 4/17 | 10/90 |
| Sequences . | Change . | CLL subset, n/N . | CLL heterogeneous, n/N . | Non-CLL, n/N . |
|---|---|---|---|---|
| IGHV1-2*02 sequences: IMGT-HFR2, codon 55 | W to R | Subset 1: 6/15 | 0/30 | 17/119 |
| IGHV1-2*02 sequences: IMGT-HFR2, codon 55 | W to R | Subset 28: 4/4 | 0/30 | 17/119 |
| IGHV3-21 sequences | Subset 2 | |||
| IMGT-HCDR1, codon 32 | S to T* | 11/56 | 6/29 | 12/95 |
| IMGT-HCDR1, codon 34 | S to N* | 9/56 | 2/29 | 7/95 |
| IMGT-HCDR2, codon 61 | S deletion | 18/56 | 0/29 | 1/95 |
| IMGT-HFR3, codon 66 | Y to H | 7/56 | 2/29 | 3/95 |
| IGHV4-34 sequences | Subset 4 | |||
| IMGT-HCDR1, codon 28 | G to D | 5/20 | 0/108 | 6/320 |
| IMGT-HCDR1, codon 28 | G to E | 8/20 | 6/108 | 18/320 |
| IMGT-HCDR1, codon 32 | G to D* | 7/20 | 20/108 | 49/320 |
| IMGT-HFR2, codon 40 | S to T | 10/20 | 29/108 | 45/320 |
| IMGT-HFR2, codon 45 | P to S | 10/20 | 17/108 | 33/320 |
| IGHV4-34 sequences | Subset 16 | |||
| IMGT-HCDR1, codon 28 | G to E | 6/7 | 6/108 | 18/320 |
| IMGT-HFR2, codon 40 | S to T | 4/7 | 29/108 | 45/320 |
| IMGT-HFR2, codon 45 | P to S | 3/7 | 17/108 | 33/320 |
| IGHV4-4 sequences | Subset 14 | |||
| IMGT-HCDR1, codon 33 | S to N | 3/4 | 0/17 | 8/90 |
| IMGT-HFR2, codon 40 | S to T | 4/4 | 4/17 | 12/90 |
| IMGT-HCDR2, codon 57 | Y to H | 4/4 | 3/17 | 7/90 |
| IMGT-HCDR2, codon 58 | H to P | 3/4 | 0/17 | 0/90 |
| IMGT-HFR3, codon 78 | I to M | 4/4 | 6/17 | 8/90 |
| IMGT-HFR3, codon 92 | S to N | 3/4 | 4/17 | 10/90 |
The frequency of changes among mutated sequences using the same IGHV gene was recorded in CLL sequences with stereotyped HCDR3s (sequences belonging to subsets), CLL sequences with heterogeneous HCDR3s, and sequences from normal or autoreactive clones. For this comparison, non-CLL sequences were pooled regardless origin (ie, whether they derived from normal or autoreactive B cells). Full details about non-CLL sequences (including origin) are provided in Tables S1 and S12.
These mutations, although very frequent among sequences of a subset, were also identified at a high frequency among either CLL sequences with heterogeneous HCDR3 or non-CLL sequences and, thus, were not considered as “subset-biased.”