Human lymphocyte proliferative response to a sporozoite T cell epitope correlates with resistance to falciparum malaria.
Human lymphocyte proliferative response to a sporozoite T cell epitope correlates with resistance to falciparum malaria.
复制标题
人类淋巴细胞对子孢子 T 细胞表位的增殖反应与对恶性疟疾的抵抗力相关。
作者：
S. Hoffman;C. Oster;Carl J. Mason;J. C. Beier;James A. Sherwood;Ballou Wr;Mutuma Mugambi;J. Chulay
为了鉴定恶性疟原虫环子孢子（CS）蛋白上疫苗相关的T细胞表位，研究了28名肯尼亚成年人对10种CS蛋白衍生肽的淋巴细胞增殖反应，并将其与抗疟能力相关联。8肽，其中6个不重叠，诱导淋巴细胞增殖从1至5名志愿者，这表明无论是遗传限制的反应，每个T表位，或优势的一些T位点上的免疫子孢子。28名志愿者的疟疾被彻底治愈，在接下来的126天里，28人中有25人再次感染。抗疟疾与抗疟疾抗原抗体无关，但与CS蛋白残基361-380和371-390的淋巴细胞反应显著相关。在25名再次感染疟疾的志愿者中，只有两名志愿者的淋巴细胞对包括恶性疟原虫CS蛋白残基361-380的肽有反应，只有一名志愿者对肽371-390有反应。相比之下，来自所有三名未被感染的志愿者的淋巴细胞对肽361-380有反应（p = 0.003），来自三名志愿者中的两名的淋巴细胞对肽371-390有反应（p = 0.023）。对肽361-380和371-390的增殖与对疟疾的抗性之间的显著相关性表明，这些重叠肽内的至少一个表位参与保护性细胞免疫应答。数据支持在未来的CS蛋白疫苗中纳入这些残留物。
To identify vaccine relevant T cell epitopes on the circumsporozoite (CS) protein of Plasmodium falciparum, the lymphocyte proliferative responses to 10 CS protein derived peptides were studied in 28 adult Kenyans, and correlated with resistance to malaria. Eight peptides, six of which were not overlapping, induced proliferation of lymphocytes from one to five volunteers, suggesting either genetic restriction of response to each of the T epitopes, or dominance of some T sites on the immunizing sporozoites. The 28 volunteers were radically cured of malaria and during the next 126 days 25 of the 28 were reinfected. Resistance to malaria was not correlated with antibodies to malaria Ag, but was significantly correlated with lymphocyte responses to CS protein residues 361-380 and 371-390. Among the 25 volunteers who became re-infected with malaria, lymphocytes from only two responded to a peptide including residues 361-380 of the P. falciparum CS protein, and only one to peptide 371-390. In contrast, lymphocytes from all three volunteers who did not become infected responded to peptide 361-380 (p = 0.003), and lymphocytes from two of the three responded to peptide 371-390 (p = 0.023). The significant correlation between proliferation to peptides 361-380 and 371-390 and resistance to malaria suggests that at least one epitope within these overlapping peptides is involved in a protective cellular immune response. The data support inclusion of these residues in future CS protein vaccines.