Troye-Blomberg M, Riley E M, Perlmann H, Andersson G, Larsson A, Snow R W, Allen S J, Houghten R A, Olerup O, Greenwood B M
Department of Immunology, University of Stockholm, Sweden.
J Immunol. 1989 Nov 1;143(9):3043-8.
The C-terminal (3') amino acid repeat region of the Plasmodium falciparum Ag Pf155/RESA, a vaccine candidate, contains immunodominant T and B cell epitopes. In order to identify additional T cell epitopes in the molecule, synthetic peptides corresponding to the centrally (5') located repeat region, as well as to four nonrepeated regions, were synthesized. T cells from 46 P. falciparum-primed individuals living in a holoendemic area of The Gambia where malaria transmission is seasonal were tested for their responsiveness to the peptides by thymidine incorporation and IFN-gamma release. There was a considerable variation in the response to different peptides. Proliferation and IFN-gamma release were not correlated in individual donors, underlining the importance of measuring both activities when screening donor populations for total T cell responsiveness to a given Ag. Whereas 72% of the donors responded with proliferation and/or IFN-gamma release to the intact protein the mean % responders to the peptides was 40%. The most frequent responses (up to 60%) were induced with peptides from the 3'- and 5'-repeat region of the protein. Analysis of some closely related sequences in the 3'-repeat region indicated that they contained at least two epitopes that were either distinct or cross-reacting in different donors, suggesting difference in the genetic control of these responses. When the same peptides were investigated for reactivity with antibodies, the best T cell inducing sequences also displayed the best antibody reactivities. However, in individual donors, T and B cell responses were not correlated. T cell responses were shown to persist after a period with no P. falciparum transmission, whereas antibody concentrations tended to decrease, suggesting differences in the requirements of boosting at the T and B cell levels, respectively.
恶性疟原虫抗原Pf155/RESA的C末端（3'）氨基酸重复区域是一种候选疫苗，包含免疫显性T细胞和B细胞表位。为了鉴定该分子中其他的T细胞表位，合成了与位于中央（5'）的重复区域以及四个非重复区域相对应的合成肽。对生活在冈比亚疟疾传播呈季节性的高度流行地区、曾感染过恶性疟原虫的46名个体的T细胞，通过掺入胸苷和释放γ干扰素来检测其对这些肽的反应性。对不同肽的反应存在相当大的差异。在个体供体中，增殖和γ干扰素释放不相关，这突出了在筛选供体群体对给定抗原的总T细胞反应性时同时检测这两种活性的重要性。虽然72%的供体对完整蛋白有增殖和/或γ干扰素释放反应，但对肽的平均反应供体百分比为40%。最常见的反应（高达60%）是由该蛋白3'和5'重复区域的肽诱导的。对3'重复区域中一些密切相关序列的分析表明，它们至少包含两个在不同供体中要么不同要么交叉反应的表位，这表明这些反应的遗传控制存在差异。当研究相同的肽与抗体的反应性时，诱导T细胞反应最佳的序列也表现出最佳的抗体反应性。然而，在个体供体中，T细胞和B细胞反应不相关。T细胞反应在无恶性疟原虫传播一段时间后仍持续存在，而抗体浓度则趋于下降，这分别表明在T细胞和B细胞水平上增强免疫的需求存在差异。
