Ia. Haagen et al., INTERACTION OF HUMAN MONOCYTE FC-GAMMA RECEPTORS WITH RAT IGG2B - A NEW INDICATOR FOR THE FC-GAMMA-RIIA (R-H131) POLYMORPHISM, The Journal of immunology, 154(4), 1995, pp. 1852-1860
Rat mAbs receive considerable interest for immunologic intervention in
man. The rat IgG2b isotype has previously been found to be optimally
active both in vivo and in vitro. We found that both a rat IgG2b CD3 m
Ab and a monovalent hybrid rat IgG2b-mouse IgG1 bispecific Ab triggere
d T cell activation in PBMC. Inhibition analyses with mAb blocking dif
ferent human IgG Fc receptors (Fc gamma R) showed a dimorphic pattern.
In donors expressing an Fc gamma RIIa-R/R131 allotype (previously def
ined on the basis of interaction with mouse (m) IgG1 as ''high respond
er'') anti-Fc gamma RI mAb 197 inhibited rat IgG2b induced T cell mito
genesis almost completely. In Fc gamma RIIa-H/H131 (''low responder''
allotype) donors, however, both anti-Fc gamma RI mAb 197 and anti-Fc g
amma RII mAb IV.3 were essential for optimal inhibition of mitogenesis
. T cell proliferation experiments performed with the use of Fc gamma
R-transfected fibroblasts as accessory cells showed the high affinity
Fc gamma RIa (CD64) to interact with both rat IgG2b and rat IgG2b-mlgG
1 hybrid CD3 mAb. The use of the two types of Fc gamma RIIa (CD32)-tra
nsfectants instead showed rat IgG2b CD3 mAb to interact solely with th
e IIa-H/H131 allotype. Interestingly, rat IgG2b-mlgG1 hybrid mAb did n
ot interact effectively with this low affinity Fc gamma R. This sugges
ts a requirement for only one rat IgG2b H chain for Fc gamma RIa-media
ted binding, whereas two identical H chains seem to be necessary for p
roper interaction with Fc gamma RIIa. Ab-sensitized RBC-rosette experi
ments performed with the use of a rat IgG2b anti-NIP mAb confirmed the
interaction pattern observed with rat CD3 mAb, supporting the phenome
na to be isotype-, and not mAb-, dependent. These analyses point to a
unique reactivity pattern for rat IgG2b Abs, interacting both with the
high affinity Fc gamma RIa in all donors and Fc gamma RIIa of individ
uals expressing the IIa-H131 allotype.