II . Expression of An t i - H - 2 K k Idiotypes on Antibodies Induced by Ant i - Id iotype or H - 2 K k Ant igen

Anti-idiotypic reagents (anti-Id) have been used to manipulate both idiotype (Id) expression and antigen-binding activity of immunized animals in various experimental systems (I-I0). In many studies, in vivo administration of small amounts of purified anti-Id has been shown to suppress subsequent immune responses to the immunogen (2-5). In contrast, evidence for induction of Id-positive molecules and antigen-specific cells in mice treated with anti-Id antibodies in the presence (3, 6, 8, 10) or absence (1, 7, 9) of antigen has also been reported. Attempts have been made to extend these studies to the production of anti-idiotypic antibodies directed against alloantisera and/or alloimmune cell populations (11-13) and to use these anti-Id to manipulate in vivo responses (14-15). This approach has led to variable success, in part, because of difficulties in reproducibly generating anti-Id antisera by these methods, possibly because of the heterogeneity of many anti-major histocompatibility complex (MHC) responses (13). We have therefore recently developed heterologous anti-idiotypic antisera raised against monoclonal anti-H-2K k antibodies. This approach offers the advantages of reproducibility and availability of large quantities of immunogen for anti-Id production (16). These anti-Id have previously been shown (7, 16) to detect "private" determinants restricted to the monoclonal reagent used as immunogen and expressed in low, often undetectable levels in alloantisera containing antibodies with the same H-2 reactivity. We examined the effects of in vivo administration of these anti-Id. We report the induction of both Id-positive molecules and antigen-binding activity as a result of such treatment. The genetic requirements for such responses and the effects of pretreatment with anti-Id on the expressed repertoire of anti-H-2K k antibodies induced after subsequent immunization to alloantigen are also described.