PART I. Peptide ImmunotherapyNatural and Autoantibodies to Human T-Cell Receptor Vβ Segments: Potential Roles in Immunomodulation

Abstract

Although the manifestation of inflammatory autodestructive disease is the result of major immunological dysfunction, recent evidence indicates that the immune system attempts to compensate by the production of immunomodulatory autoantibodies. Healthy humans have low levels of naturally occurring autoantibodies directed against the first complementarity-determining region (CDR1) and third framework region (FR3) of their own T-cell receptor (TCR) Vβ segments, but individuals suffering from rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) can have highly elevated levels of these autoantibodies. We cloned and characterized human anti-TCR monoclonal autoantibodies (mAAbs) from RA and SLE patients. Because of the cross-reactions between distinct CDR1 segments of human TCR Vβ and corresponding murine homologs, it was possible to show that human mAAbs blocked the capacity of a murine TH1 cell line (DO11.10) to produce IL-2 in response to antigenic stimulation in vitro. These results support the hypothesis that autoantibodies against TCR Vβ can shut down TH1-mediated inflammatory autodestructive reactions.