1588 Recognition of Variable Domains of a Mouse Myeloma

A basic assumption of Jerne's network theory (1) is that the immune system of an individual can recognize its own antigen receptors. Because this concept opens many possibilities for immunological manipulation (2), it is important to ascertain whether the immune system recognizes its own immunoglobulin (Ig) variable (V) 1 domains in a way that conforms to the experience gained with conventional extrinsic protein antigens. To this end we have been studying the antigenicity of the hapten(dinitrophenyt [DNP]-lysine) binding IgA mouse myeloma protein 315. The amino acid sequences of the entire L-315 and the V region of the H-315 (VH-315) chains have been determined (3, 4). From these data it is clear that L-315 belongs to the rare ~2-type, found in ~ 1% of normal Ig in most strains of mice (5). The mouse ~ genes are arranged in two clusters on the chromosome: V~l, Ja, Ca, J1, C1 and VX2, J2, C2, J4, C4 (6). o f the three Ig multigene families in the mouse, the ~ gene family thus has the smallest number of V genes, i.e., only two. The immune response of BALB/c mice to M315 was first studied by Sirisinha and Eisen (7), who demonstrated that M315 mixed with Freund's complete adjuvant elicited antibodies specific for an antigenic determinant that was only expressed when H-315 and L-315 chains were assembled, and that was intimately associated with the hapten binding site. Work carried out in this laboratory (8) has revealed that immunization with affinity-labeled M315 (DNP-lysine covalently attached in the combining site) induced antibodies that recognized determinants which also required assembled H + L chains, but which were located outside the combining site, because the antibodies formed complexes with M315 in the presence of a high concentration of DNP-lysine. Furthermore, the free form of native 2~-315 evoked antibodies that bound free but not assembled ~2 of the complete M315 (9). In contrast, carrier-specific helper T cells primed with free h2-315 or its V domain (Vh2) responded to a boost with the complete M315 (10), suggesting that cellular and humoral immunity elicited