D. Haddad et al., DIFFERENTIAL INDUCTION OF IMMUNOGLOBULIN-G SUBCLASSES BY IMMUNIZATIONWITH DNA VECTORS CONTAINING OR LACKING A SIGNAL SEQUENCE, Immunology letters, 61(2-3), 1998, pp. 201-204
The route and method used to immunize mice with antigen-expressing DNA
plasmids have an impact on the resulting T-helper cell response and I
gG subclass distribution. Previous findings further indicate that the
intracellular targeting of expressed antigens influences the different
ation of naive T-cells into either a Th1 or a Th2 type of response. In
the present study, we analyzed the levels of IgG1 and IgG2a antibodie
s, as correlates of Th2 and Th1 responses, respectively, after intramu
scular injection of mice with plasmids encoding a chimeric protein con
taining a Plasmodium falciparum blood stage antigen expressed in two d
ifferent forms. One plasmid expresses the antigen in a secreted form a
s it is preceded by a signal sequence while expression from the other
plasmid, lacking this sequence, results in cytoplasmic localization of
the antigen. Mice immunized with the plasmid encoding secreted antige
n responded with predominantly IgG1 antibodies. In contrast, sera from
mice immunized with the plasmid expressing cytosolic protein displaye
d a mixed IgG1/IgG2a profile. In line with previous findings, our resu
lts suggest that the intracellular targeting of proteins expressed by
DNA plasmids is an important factor for the differentation of Th cells
and the resulting subclass pattern of IgG responses. (C) 1998 Elsevie
r Science B.V. All rights reserved.