The production of antibodies against poorly immunogenic proteins is problem
atic. Often there is a failure to generate such antibodies. Furthermore, an
tibodies against other specificities are frequently induced. We describe a
simple approach, analogous to conjugation to a protein carrier, whereby imm
unization with naked DNA was used to raise antibody to a highly homologous
and poorly immunogenic allotypic protein. Deoxyribonucleic acid encoding th
e protein of interest was fused to DNA encoding the Fc region of a foreign
Ig, resulting in increased immunogenicity. The potential applications of th
is approach include the production of antisera and mAb to allotypic variant
s, mutant proteins, and proteins that are highly conserved between species.