IDIOTYPIC RECEPTORS FOR ANTIGEN ON T LYMPHOCYTES

Abstract

It is possible to use the antigen-binding receptors on T lymphocytes as immunogen, thereby inducing anti-T idiotypic antibodies. A convenient way to do this is to use F1-hybrid animals between two inbred strains as recipients of T lymphocytes from one of the parental strains. Such F1-hybrid animals will then frequently produce anti-idiotypic antibodies specific for T cell receptors on the inoculated cells having specificity for the major histocompatibility locus antigens of the other parent. We have used such an approach in inbred rat strains differing at the Ag-B locus. Antibodies induced in such a manner against T receptors for antigen cross-react completely with idiotypes present on IgG antibodies directed against the same antigen as the T receptors. Thus, antigen-binding receptors of T and B lymphocyte type express shared idiotypes indicating the use of common genetic material in the generation of their respective receptors. It is possible to directly visualize the idiotype-positive T cells by the use of anti-idiotypic antibodies. In the present system between 5–6% of normal T lymphocytes express idiotypic receptors signifying immune reactivity across the Ag-B locus barrier. Proof for actual linkage between idiotype and specific immune potential came via affinity chromatography of idiotype-positive cells using anti-idiotype antibodies, whereby close to “pure” idiotype-positive T cells could be demonstrated to express highly restricted immune reactivity against the relevant Ag-B antigen only. Such a high figure of idiotype-positive cells suggested the presence of “natural” antibody-like molecules to be present in normal serum from adult rats due to membrane turnover or shedding. It was possible to demonstrate and actually isolate such molecules being present in very low concentration in serum as well as in urine. Analysis as to molecular characteristics of the natural antibodies in serum revealed two dominant groups of molecules, both expressing idiotypic markers and antigen-binding capacity. One, around 150,000 daltons, and one with a molecular size of around 35,000 daltons. The smaller molecules were also found in the urine. When analyzed as to cellular origin the large molecules were found to be produced by B lymphocytes, whereas the smaller ones were a product of T cells.