The Influence of Epitope Density on the Immunological Properties of Hapten‐Protein Conjugates

The influence of epitope density on the induction of hapten‐specific (B‐cell) tolerance by dinitrophenytated bovine serum albumin (DNP.BSA) was investigated. Mice were given multiple iniections of DNP5BSA or DNP50BSA. and tolerance was assayed by challenge with DNP.haemocyanin Under ‘conventional’ tolerance‐inducing conditions (5 mg three times a week for 2 to 8 weeks). anti‐DNP anti body formation was completely suppressed by DNP50BSA but only partially by DNP5BSA. However, with a 2‐week intensive regimen equal amounts of hapten as DNP5BSA or as DNP50BSA induced equal degrees of tolerance Since DNP50BSA is lost from the body much more slowly than DNP5BSA, these data suggest that high epitope density does not fundamentally affect the tolerogenicity of DNP.BSA. Partial tolerance preferentially suppressed IgG antibody formation to DNP.haemocyanin. whereas higher doses of DNP50BSA produced complete DNP‐specific tolerance. During spontaneous loss of tolerance the IgM response recovered more rapidly than the IgG response. These results strongly suggest that IgG precursor cells are more sensitive to tolerance induction than IgM precursors and that tolerance, once induced, is more profound in the former than in the latter.