Romero P J, Tam J P, Schlesinger D, Clavijo P, Gibson H, Barr P J, Nussenzweig R S, Nussenzweig V, Zavala F
Department of Medical and Molecular Parasitology, University Medical Center, Rockefeller University, New York.
Eur J Immunol. 1988 Dec;18(12):1951-7. doi: 10.1002/eji.1830181213.
The present findings establish the lack of genetic restriction of the humoral immune response to sporozoites of Plasmodium berghei, corraborating earlier observations that mice of different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti-sporozoite antibodies are directed against the repetitive B cell epitope of the circumsporozoite (CS) protein. However, neither a peptide containing a dimer of this repeat (17.1), nor a peptide polymer containing multiple repeats induced an antibody response in mice of different H-2 and different genetic backgrounds. A yeast-derived recombinant, containing the repeat domain and part of the surrounding amino and carboxy-terminal regions of the P. berghei CS protein, induces very different levels of antibody in mice of diverse H-2 haplotypes. H-2j mice are high responders and the immunized mice are extensively protected against sporozoite challenge. The lymph node cells of the H-2j mice (but not from other strains) proliferated in the presence of peptide N, contained in the amino terminal region of the CS recombinant. Additional H-2-restricted T cell epitopes have been identified in amino and carboxy-terminal regions of the CS protein, and mice of most of the strains recognized multiple T cell epitopes. Two peptides representing T cell epitopes were synthesized in tandem with a peptide representing the B cell epitope, and were assayed for T helper activity in vivo. The antibody response of mice, primed by a single injection of sporozoites, was boosted very effectively by the administration of peptide N + 17.1 or peptide B-4 + 17.1. The B-4 T cell epitope is located in the carboxy-terminal region of the CS protein and is recognized by mice of at least four different H-2 haplotypes. These observations demonstrate that the immune response to the CS protein of P. berghei is not genetically restricted and that it contains several T cell epitopes, some of which can function as helper epitopes. In addition, they show that a synthetic sporozoite vaccine can boost the immune response to sporozoites.
目前的研究结果证实，针对伯氏疟原虫子孢子的体液免疫反应不存在遗传限制，这与早期的观察结果相符，即不同品系的小鼠可以通过用辐照子孢子免疫得到保护。大多数（如果不是全部）抗子孢子抗体都针对环子孢子（CS）蛋白的重复B细胞表位。然而，无论是含有该重复序列二聚体的肽（17.1），还是含有多个重复序列的肽聚合物，都不能在不同H-2和不同遗传背景的小鼠中诱导抗体反应。一种酵母衍生的重组体，包含伯氏疟原虫CS蛋白的重复结构域以及部分周边的氨基和羧基末端区域，在不同H-2单倍型的小鼠中诱导出非常不同水平的抗体。H-2j小鼠是高反应者，免疫后的小鼠能广泛抵抗子孢子攻击。H-2j小鼠（而非其他品系）的淋巴结细胞在CS重组体氨基末端区域所含的肽N存在时会增殖。在CS蛋白的氨基和羧基末端区域还鉴定出了其他H-2限制性T细胞表位，大多数品系的小鼠都能识别多个T细胞表位。将代表T细胞表位的两种肽与代表B细胞表位的肽串联合成，并在体内检测其T辅助活性。单次注射子孢子致敏的小鼠，通过给予肽N + 17.1或肽B-4 + 17.1能非常有效地增强抗体反应。B-4 T细胞表位位于CS蛋白的羧基末端区域，至少有四种不同H-2单倍型的小鼠能识别它。这些观察结果表明，针对伯氏疟原虫CS蛋白的免疫反应不存在遗传限制，且包含多个T细胞表位，其中一些可作为辅助表位。此外，它们还表明合成子孢子疫苗可以增强对子孢子的免疫反应。
