Immune response to a molecularly defined internal image idiotope

A monoclonal anti-idiotope termed 87.92.6 mimics the neutralization/cell-attachment site of the reovirus type 3 hemagglutinin (HA3). The second complementarity determining regions of the VH and VL of 87.92.6 share sequence similarity with a determinant on the HA3. We have used synthetic peptides (termed VH, VL, and Reo peptides, respectively) to probe the immunologic significance of this sequence similarity. Antibodies specific for Reo peptide or VL peptide neutralized reovirus type 3 infectivity. Although Reo peptide was an effective immunogen by itself, free VL peptide or VH peptide were unable to elicit antibodies unless they were linked to each other (VH-VL peptide). Immunization with reo peptide, 87.92.6, or the HA3 elicited a specific lymphocyte proliferative response to VH peptide, indicating that VH peptide may bear an important TH determinant. As found previously for 87.92.6, VL peptide elicited a delayed-type hypersensitivity response specific for reovirus type 3. Reovirus type 3 specific cytolytic lymphocytes specifically lysed targets coated with VH-VL peptide, but not VH or VL peptide alone. These results suggest that immune cross-reactivity between an external Ag and an internal image antibody can be understood at the primary structural level. These observations may have important implications for understanding the development of autoantibodies, network interactions, and the regulation of immune responses.