Rat alloantisera were prepared in inbred strains of rats by immunization with lymphoid cells of a donor strain. Six host-donor combinations were incompatible at the major (AgB or H-1) as well as other histocompatibility loci. These sera contained complement dependent cytotoxins after two injections of 1 to 3 × 107 cells. Titrations showed 100% kill at several antibody (ab) concentrations and a typical doubling dilution end point. Six host-donor combinations were incompatible only at non-AgB (non-H-1) loci. These sera contained cytotoxins only after two injections of 4 × 108 cells. Titrations showed end points equal to those of the first group of antisera but no concentration was able to kill 100% of available target cells, nor did increments in antiserum concentration yield any change in the low number of cells killed. These characteristics were not the result of: a) the injection schedule; b) presence of complement inhibitors; c) low response capacity of the host; d) the presence of two lymphocyte subpopulations in the target cell suspension nor e) low ab concentrations. Absorption of the two types of antisera by homologous cells suggests that the non-AgB antisera: a) contain both complement-fixing (CF) and non-CF ab; b) the non-CF concentration is as much as 10-fold higher than CF; c) avidities of non-CF and CF are similar. We infer that immunization with non-AgB antigens preferentially induces formation of non-CF ab which is responsible for the odd titration and is enhancng ab.

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