IgG autoantibodies to "switch peptide" determinants of TCR alpha/beta in human pregnancy.

The fetus is a natural allograft that is protected from immunologic rejection by a complex set of structural and regulatory mechanisms. We determined whether healthy pregnant women differed significantly from healthy non-pregnant controls in their capacity to produce autoantibodies 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 containing the complete V alpha/V beta structures, analysis of comparative reactivity against individual peptide segments of the molecules, indicated enhanced reactivity to regions corresponding to the CDR1 of the alpha chain and to the Fr3 of the variable region of the beta chain. A major difference was noted by increased reactivity of IgG autoantibodies of pregnant women to peptides corresponding to the "switch" region joining the variable and constant domains. This was noted with both the Tcr alpha and beta chains and was directed against highly conserved determinants 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 the suppression of T-cell reactivity of fetal determinants.