Löwenadler B, Lycke N, Svanholm C, Svennerholm A M, Krook K, Gidlund M
Kabi Pharmacia Biopharma AB, Kabigen, Stockholm, Sweden.
Mol Immunol. 1992 Oct;29(10):1185-90. doi: 10.1016/0161-5890(92)90054-2.
The ability of a T helper (Th) epitope to induce help for B cells recognizing different determinants within a multideterminant antigen was investigated. Chimeric fusion proteins, containing inserts of single or multiple copies of the Th epitope ovalbumin 323-339 (ova) at two different positions, were compared with respect to their ability to induce specific antibody production and ova-specific T cell activation. The antibody responses against B cell determinants at the amino and carboxy terminus, respectively was differently influenced by the molecular positioning of the inserted Th determinant. All ova-containing fusion proteins induced antibody production against the B cell determinant at the amino terminal end irrespective of the positioning of ova. In addition, multiple copies of ova in any position led to increased levels of antibody production against this epitope. In contrast, T cell help for antibody production against the determinant at the carboxy terminus was more effective after insertion of multiple copies of ova in a distal than in an adjacent position. Furthermore a fusion protein, containing four copies of ova effectively elicited T cell help for high levels of antibody production against both examined B cell determinants, showing that activated Th cells recognizing a single epitope could simultaneously provide help for distinct sets of B cells specific for widely separated epitopes within a protein. Immunodominant T cell recognition of ova in all chimeric peptides, independently of its position, was demonstrated by lymph node cell (LNC) proliferation of primed BALB/c mice. The level of ova-specific T cell proliferation was similar, irrespective of which chimeric peptide that had been used for priming, and thus did not reveal any differences in T cell priming efficiencies related to the number of ova copies in the fusion proteins. However, when the peptides were presented to a ova-specific T cell line by A20 B lymphoma cells, a close correlation between IL-2 production by the clonal T cells and the number of ova epitopes in the chimeric peptides was observed. Thus, increased cytokine production by ova-specific T cells may be important for the increased level of in vivo antibody production observed in response to multiple copies of ova in the chimeric antigens.
研究了辅助性T（Th）表位诱导对识别多表位抗原内不同决定簇的B细胞提供辅助的能力。将含有Th表位卵清蛋白323 - 339（ova）单拷贝或多拷贝插入物的嵌合融合蛋白，分别置于两个不同位置，比较它们诱导特异性抗体产生和ova特异性T细胞活化的能力。针对氨基末端和羧基末端B细胞决定簇的抗体反应，受插入的Th决定簇分子定位的影响不同。所有含ova的融合蛋白，无论ova的定位如何，均能诱导针对氨基末端B细胞决定簇的抗体产生。此外，任何位置的多个ova拷贝都会导致针对该表位的抗体产生水平增加。相比之下，在远端插入多个ova拷贝比在相邻位置插入时，针对羧基末端决定簇的抗体产生的T细胞辅助更有效。此外，一种含有四个ova拷贝的融合蛋白有效地引发了T细胞辅助，以产生针对两个检测的B细胞决定簇的高水平抗体，表明识别单个表位的活化Th细胞可以同时为蛋白质内广泛分离表位特异性的不同B细胞集提供辅助。通过致敏BALB/c小鼠的淋巴结细胞（LNC）增殖，证明了所有嵌合肽中ova的免疫显性T细胞识别，与用于致敏的嵌合肽无关，ova特异性T细胞增殖水平相似，因此未揭示与融合蛋白中ova拷贝数相关的T细胞致敏效率的任何差异。然而，当A20 B淋巴瘤细胞将这些肽呈递给ova特异性T细胞系时，观察到克隆T细胞产生的IL - 2与嵌合肽中ova表位数量之间密切相关。因此，ova特异性T细胞增加的细胞因子产生，对于嵌合抗原中多个ova拷贝所观察到的体内抗体产生水平增加可能很重要。
