Abstract
Among the self antigens, immunoglobulins, and in particular idiotypes, are of special interest because of their extreme sequence heterogeneity and their postulated involvement in Regulatory interactions in the immune system. We have therefore studied antigen processing and presentation of variable Region peptides, processed idiotypes, to MHC class II molecule-restricted T cells. The immunoglobulin used has been the λ2315 light chain produced by the BALB/c MOPC 315 plasmacytoma (α, λ2). The minimum length of a stimulatory synthetic idiotypic peptide comprises Residues 91-101 of λ2315 and is presented by the I-Ed molecule to CD4+ T cells. T cell clones with specificity for the 91-101(X2315)/I-Ed complex utilize a limited TCR Repertoire and are of both Th1 and Th2 type. For presentation, extracellular λ2315 Requires endocytosis and processing, as previously described for conventional exogenous antigens. In addition, a B lymphoma cell can process and present its own endogenous λ2315. This was shown by transfecting manipulated λ2315 gene variants into B lymphoma cells, followed by evaluation of the APC function of the transfectants. These studies demonstrated that surface expression or secretion of λ2315 is not necessary for presentation and suggested that the endoplasmic Reticulum may be a processing compartment. To extend our findings to naive Id+ B cells and anti-Id T cells, we have generated λ2315-transgenic as well as TCR-transgenic mice. A model is presented for a T-B cell interaction based on presentation of processed idiotypes.