Table 8.
IMGT nomenclature, Eu positions and IMGT motif of engineered Fc variants involved in complement-dependent cytotoxicity (CDC) enhancement (Effector #4).
| IMGT Engineered Variant Name | IMGT Engineered Variant Definition | IMGT Amino Acid Changes on IGHG CH Domain (Eu Numbering between Parentheses) | Amino Acid Changes with the Eu Positions | Motif Identifiable in Gene and Domain with Positions According to the IMGT Unique Numbering and with Eu Positions between Parentheses | 1. Property and Function | 2. Property and Function |
|---|---|---|---|---|---|---|
| G1v5 |
CH2
W109 |
CH2 K109 > W (326) |
K326W |
IGHG1 CH2 FG 105–117 (322–332) KVSNKA..LPAPI > KVSNWA..LPAPI |
CDC enhancement. Increases C1q binding [102] |
ADCC reduction [102]. |
| G1v15 |
CH2
S118 |
CH2 E118 > S (333) |
E333S |
IGHG1 CH2 FG 105–117,118 (322–333) KVSNKA..LPAPIE > KVSNKA..LPAPIS |
CDC enhancement. Increases C1q binding [102] |
|
| G1v16 |
CH2
W109, S118 |
CH2 K109 > W (326), E118 > S (333) |
K326W, E333S |
IGHG1 CH2 FG 105–117,118 (322–333) KVSNKA..LPAPIE > KVSNWA..LPAPIS |
CDC enhancement. Increases C1q binding [102] |
|
| G1v17 |
CH2
E29, F30, T107 |
CH2 S29 > E (267), H30 > F(268), S107 > T (324) |
S267E, H268F, S324T EFT |
IGHG1 CH2 27–31 (265–269) DVSHE > DVEFE FG 105–117 (322–332) KVSNKA..LPAPI > KVTNKA..LPAPI |
CDC enhancement Increases C1q binding [112] |
|
| G1v18 |
CH3
R1, G109, Y120 |
CH3 E1 > R (345), E109 > G (430), S120 > Y (440) |
E345R, E430G, S440Y |
IGHG1 CH3 1.4–2 (341–346) GQPREP > GQPRRP 105–110 (426–431) SVMHEA > SVMHGA 118–125 (438–445) QKSLSLSP > QKYLSLSP |
CDC enhancement. Increases C1q binding [113]. The triple mutant IgG1-005-RGY (IGHG1v18) form IgG1 hexamers [113] |
Favors IgG1 hexamerization. |
| G1v35 |
CH2
E29 |
CH2 S29 > E (267) |
S267E SE |
IGHG1 CH2 27–31 (265–269) DVSHE > DVEHE |
CDC enhancement. Increases C1q binding [112] |
Binds to FCGRT and FcγRIIB, but not to other FcγR in a mouse model [114]. |
| G1G3v1 |
CH2
Q38, K40, F85.2 |
CH2 K38 > Q (274), N40 > K (276), Y85.2 > F (300) |
K274Q, N276K, Y300F chimere G1–G3 (1) |
IGHG1 CH2 34–41 (270–277) DPEVKFNW > DPEVQFKW 84.1–85.1 (294–301) EQYNSTYR > EQYNSTFR |
CDC enhancement. Increases C1q binding [115]. |
|
| G4v2 |
CH2
P116 |
CH2 S116 > P(331) |
S331P |
IGHG4 CH2 FG 105–117 (322–332) KVSNKG..LPSSI > KVSNKG..LPSPI |
CDC enhancement [116]. (G1-, G2-, G3-like). |
(1) The chimeric chain is the IGHG1*01 CH1-hinge—IGHG3*01 CH2-CH3. Amino acids Q38, K40 (CH2) and F85.2 (CH3) are from IGHG3*01. The changes are shown in comparison to the IGHG1*01 amino acids at the same positions as K38, N40 (CH2) and Y85.2 (CH3).