Anti-clonotypic autoantibodies in pregnancy

Abstract

Idiotypic T-cell receptors for antigen have been identified in previous studies by use of anticlonotypic monoclonal antibodies. To determine whether anti-receptor autoantibodies play a role in immune regulation, we have used normal pregnancy as a model. T-cell clones were generated from the peripheral blood of a primiparous woman by priming her lymphocytes to stimulating cells from her husband. As a control, T cells primed to lymphocytes from HLA different controls were used. Purified IgG was prepared from this woman's serum and tested for its reactivity with cell surface antigens expressed by autologous T-cell clones. We have identified one anti-HLA-DR reactive clone specific for the immunizing HLA haplotype of the child that reacted with autologous F(ab′) 2 in immunofluorescence studies. When tested in functional studies, the F(ab′) 2 blocked the capacity of the clone to lyse specific target cells, while triggering clonal proliferation in the absence of stimulating cells. The determinant(s) recognized by autoantibodies in the F(ab′) 2 preparation comodulate with the T3 antigen present on the surface of the cells. These data suggest that sera obtained during pregnancy contain autoantibodies which behave similarly to heterologous anti-clonotypic antibodies. Such anti-T-cell receptor antibodies may play a role in maternal tolerance to the fetus.