Zöller M, Andrighetto G
Institute of Nuclear Medicine, German Cancer Research Center, Heidelberg, FRG.
Scand J Immunol. 1987 Sep;26(3):277-86. doi: 10.1111/j.1365-3083.1987.tb02261.x.
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.
半抗原表位对载体特异性应答调节的影响在疫苗接种和异源化方案中具有重要意义。通过分析在半抗原表位（三硝基苯酚，TNP）影响下的初次和二次抗马红细胞（HRBC）应答来模拟这种情况。在TNP存在的情况下，初次和二次抗HRBC应答减弱。在TNP存在时，针对载体的初次应答延迟，并且与HRBC相比，对TNP-HRBC的初次和二次抗载体应答消失得更快。当在有限稀释（LD）条件下测定HRBC特异性B细胞的频率时，发现与HRBC相比，在TNP-HRBC存在时HRBC特异性B细胞的频率较低。因此，用HRBC免疫后，B细胞频率增加了49倍，而用TNP-HRBC免疫后，频率仅增加了11倍。此外，半抗原表位通过调节元件影响抗载体应答。在生理条件下，半抗原特异性辅助不足，半抗原特异性B细胞竞争载体特异性辅助性T细胞（TH）。在半抗原-载体免疫的小鼠中，抑制作用比载体免疫的小鼠更有效，与此观察结果一致，当使用TNP-HRBC而非HRBC作为抗原时，在LD培养物中观察到抑制性T细胞（Ts）频率增加。得出的结论是，半抗原表位与抗载体应答相关，因为半抗原特异性B细胞竞争载体特异性辅助，半抗原特异性抑制下调载体特异性辅助，并且半抗原可能掩盖载体的免疫原性表位，导致B细胞库的不完全激活。
