Naturally occurring human autoantibodies to defined T-cell receptor and light chain peptides

We used synthetic peptides duplicating the structures of a human lambda light chain (Mcg), and a human T-cell receptor (Tcr) alpha and a Tcr beta chain predicted from gene sequence to determine the presence and loci of activity of natural human autoantibodies directed against these antigen recognition molecules. We report that normal individuals and patients suffering from autoimmune diseases have antibodies directed against regions of lambda light chains and Tcr beta chains corresponding to the first complementarity determining region and the third framework region of the variable domain and to constant region determinants. The levels of IgM natural antibodies particularly against the CDR1 peptides tend to be higher in RA patients than in normals or SLE patients. Although polyclonal IgG immunoglobulins from healthy individuals did not show detectable reactivity to Tcr alpha peptides, such reactivity was found in the IgM immunoglobulins of RA patients, thereby showing that Tcr alpha peptides can be autoantigenic in man. The levels of IgM autoantibodies to V beta CDR1 peptides tend to decrease with age. By contrast, there was a marked increase in IgG natural autoantibodies to certain CDR1 sequences with advancing age. We suggest that the natural antibodies to defined regions of immunoglobulins and T-cell receptors are part of a physiological network for the regulation of the immune response.