Idiotypic Self Binding of a Dominant Germline Idiotype ( T 15 )

Recently we have described (1) an IgM antibody that has the unique property of specific self binding. The 11 E7-1 hybridoma was isolated by fusion with a nu/nu BALE/c mouse immunized with TEPC 15 myeloma protein (T15). The mAb 11 E7-1 binds to PC, to insolubilized T15, and to 11E7-1 itself. Thebinding is specifically inhibited by free PC and PC analogs . Thus, this antibody has a dual specificity of binding to PC and of expressing an idiotope for PC inhibitable self binding. Because of the simultaneous expression of complementary paratope and idiotope it has been termed "autobody" (2-4). The specificity of self binding appears to be extremely stringent, since as little as 10-7 M PC inhibits 50% self binding in ELISA. Furthermore, the strength of inhibition by PC, glycerophosphorylcholine (GPC),' and choline follows the same pattern as the PC fine specificity of T15 binding to PC (5) . This seems to suggest that the PC binding site (paratope) of 11E7-1 is similar to the paratope of the T15 prototype, and also that the PC site is directly involved in the self binding. A rational interpretation of these properties of 11 E7-1 implies that this antibody expresses a paratope for the antigen and its complementary internal image idiotope (6) . 11 E7-1 also expresses the T15 idiotype because it reacts with an anti-T 15 mAb, F6-3, that reacts with T15 idiotype-positive antibodies ofdifferent isotypes (7) . This finding led us to speculate that 11E7-1 may be part of a self-regulating idiotypic cellular loop controlling the normal anti-PC response or may cause complex deposition on pathogenic targets . Regardless of the biological meaning of a complementary self-binding antibody, this unique dual expression of paratope and idiotope has important ramifications for the network hypothesis . In this update on our studies of the 11 E7-1 autobody, we addressed the question of the structural origin of the autobody properties. The PC-specific self binding could be caused by a somatic mutation of the T15 prototype structure in which the PC paratope remained intact and an internal image idiotope has