The trimolecular complex is a cornerstone of immunologic responsiveness and includes an HLA molecule, peptide antigen, and the T cell receptor. From the point of view of transplantation in which HLA incompatibility is associated with graft rejection, how the HLA disparate fetus escapes rejection is an intriguing unsolved question of immunology. Local factors at the maternal-fetal interface are likely to be key aspects of pregnancy success. Despite local factors, however, some fetal cells escape into the maternal circulation. The striking remission during pregnancy of rheumatoid arthritis indicates that effects on the maternal system can be systemic. Rheumatoid arthritis is an autoimmune disorder and is characterized by an association with particular HLA class II alleles. We have recently demonstrated that amelioration of this autoimmune disease is associated with fetal-maternal disparity for HLA class II antigens. The results of these studies (and others) have led us to postulate that the maternal T cell repertoire undergoes changes during pregnancy in response to fetal HLA peptides that enter the maternal circulation. During the 3 to 6 months postpartum rheumatoid arthritis returns virtually without exception. We propose to test the hypothesis that significant changes occur in the maternal T cell repertoire during pregnancy and after delivery. We expect that these changes will be particularly apparent around parturition. It is the purpose of the studies described in this proposal to characterize alpha-beta and gamma-delta T cell receptor usage around parturition, before, during and after pregnancy. From the fetal perspective pregnancies of RA women are excellent. Thus this autoimmune disease affords a human model in which a systemic effect is observed during pregnancy: a model from which insights may be gained bi- directionally about an enigmatic autoimmune disease that favors women and about successful pregnancy in which the fetal allograft thrives.
