IGG AUTOANTIBODIES TO SWITCH PEPTIDE DETERMINANTS OF TCR ALPHA BETA IN HUMAN-PREGNANCY/

The fetus is a natural allograft that is protected from immunologic re jection by a complex set of structural and regulatory mechanisms. We d etermined whether healthy pregnant women differed significantly from h ealthy non-pregnant controls in their capacity to produce autoantibodi es to defined antigenic determinants of the alpha/beta T-cell receptor . Although controls and pregnant women expressed comparable levels of autoantibodies against an intact recombinant T-cell receptor containin g the complete V alpha/V beta structures, analysis of comparative reac tivity against individual peptide segments of the molecules, indicated enhanced reactivity to regions corresponding to the CDR1 of the or ch ain and to the Fr3 of the variable region of the beta chain. A major d ifference was noted by increased reactivity of IgG autoantibodies of p regnant women to peptides corresponding to the ''switch'' region joini ng the variable and constant domains. This was noted with both the Tcr or and beta chains and was directed against highly conserved determin ants within these molecules. Antibodies to this region are lacking in the non-pregnant controls. It is possible that autoantibodies directed against conserved regions of the T-cell receptor might function in th e suppression of T-cell reactivity of fetal determinants. (C) 1994 Aca demic Press, Inc.