Bush M E, Alkan S S, Nitecki D E, Goodman J W
J Exp Med. 1972 Dec 1;136(6):1478-83. doi: 10.1084/jem.136.6.1478.
L-Tyrosine-p-azobenzenearsonate (RAT) induces cellular immunity without humoral antibody in guinea pigs. Asymmetric bifunctional antigens composed of one RAT moiety and one dinitrophenyl (DNP) group separated by flexible spacers induce anti-RAT cellular immunity and an anti-DNP humoral response. Symmetrical bifunctional antigens of similar design but comprised of two RAT determinants induce cellular immunity without demonstrable anti-RAT antibody. However, when the flexible spacer is replaced by a rigid decaproline chain, humoral anti-RAT responses are provoked. Since RAT contains both electropositive (azo) and electronegative (arsonate) centers, the failure of bifunctional RAT compounds with flexible spacers to induce humoral immunity might be ascribed either to intramolecular stacking, which compromises their bifunctional character, or to interaction of both determinants with receptors on the same cell surface, which would fail to satisfy the requirement for cooperation. In order to distinguish between these alternatives, symmetrical bifunctional antigens composed of two L-tyrosine-p-azophenyltrimethylammonium (TAT) determinants separated by flexible or rigid spacers were synthesized. TAT is immunogenic and does not cross-react with RAT. Furthermore, it contains only electropositive centers and consequently bifunctional molecules do not undergo intramolecular stacking. Immunization with either flexibly or rigidly spaced bifunctional TAT antigens raised anti-TAT antibody. These results conclusively demonstrate that "self-help," cooperation between bone marrow-derived and thymus-derived lymphocytes of identical or similar specificity, can occur, provided the determinants on the antigen are prevented from associating with each other.
L-酪氨酸对氨基苯砷酸盐(RAT)可在豚鼠中诱导细胞免疫而不产生体液抗体。由一个RAT部分和一个二硝基苯基(DNP)基团通过柔性间隔臂隔开组成的不对称双功能抗原可诱导抗RAT细胞免疫和抗DNP体液反应。设计相似但由两个RAT决定簇组成的对称双功能抗原可诱导细胞免疫,但未检测到抗RAT抗体。然而,当柔性间隔臂被刚性的十脯氨酸链取代时,会引发抗RAT体液反应。由于RAT同时含有正电(偶氮)和负电(砷酸盐)中心,具有柔性间隔臂的双功能RAT化合物未能诱导体液免疫,可能是由于分子内堆积损害了它们的双功能特性,或者是由于两个决定簇与同一细胞表面的受体相互作用,无法满足协同作用的要求。为了区分这些可能性,合成了由两个L-酪氨酸对苯基三甲基铵(TAT)决定簇通过柔性或刚性间隔臂隔开组成的对称双功能抗原。TAT具有免疫原性,且与RAT无交叉反应。此外,它只含有正电中心,因此双功能分子不会发生分子内堆积。用柔性或刚性间隔的双功能TAT抗原免疫可产生抗TAT抗体。这些结果确凿地证明,只要抗原上的决定簇相互不发生关联,相同或相似特异性的骨髓来源淋巴细胞和胸腺来源淋巴细胞之间就可以发生“自助”协同作用。