Regulation of carrier-specific response via a haptenic epitope.

Influences of haptenic epitopes on the regulation of carrier-specific responses are of importance in vaccination and heterogenization protocols. This situation was modelled by analysing the primary and secondary anti-horse red blood cell (HRBC) response under the influence of a haptenic epitope (trinitrophenol, TNP). Primary and secondary anti-HRBC responses were diminished in the presence of TNP. The primary response against the carrier was delayed in the presence of TNP and primary and secondary anti-carrier responses vanished more rapidly in response to TNP-HRBC than in response to HRBC. When frequencies of HRBC-specific B cells were determined under limiting dilution (LD) conditions, a lower frequency of HRBC-specific B cells was discovered in the presence of TNP-HRBC as compared to HRBC. Accordingly, after priming with HRBC, the frequency of B cells was increased by a factor of 49, while after priming with TNP-HRBC the frequency was only increased by a factor of 11. Furthermore, haptenic epitopes influenced the anti-carrier response via regulatory elements. Under physiological conditions, hapten-specific help was insufficient and hapten-specific B cells competed for carrier-specific helper T cells (TH). Suppression was more efficient in hapten-carrier-primed mice than in carrier-primed mice and in line with this observation, an increased frequency of suppressor T cells (Ts) was observed in LD cultures when TNP-HRBC instead of HRBC were used as antigen. It is concluded that haptenic epitopes are relevant for the anti-carrier response, since hapten-specific B cells compete for carrier-specific help, hapten-specific suppression down-regulates carrier-specific help, and the hapten may hide immunogenic epitopes of the carrier, resulting in incomplete activation of the B-cell repertoire.