Connelly M, King C L, Bucci K, Walters S, Genton B, Alpers M P, Hollingdale M, Kazura J W
Division of Geographic Medicine, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4983, USA.
Infect Immun. 1997 Dec;65(12):5082-7. doi: 10.1128/iai.65.12.5082-5087.1997.
Liver-stage antigen 1 (LSA1) is one of several pre-erythrocytic antigens considered for inclusion in a multiantigen, multistage subunit vaccine against falciparum malaria. We examined T-cell proliferation and cytokine responses to peptides corresponding to amino acids 84 to 107, 1813 to 1835, and 1888 to 1909 of LSA1 in asymptomatic adults living in an area of Papua New Guinea where malaria is holoendemic. Whereas T cells from North Americans never exposed to malaria did not respond to any of the peptides, those from 52 of 55 adults from the area where malaria is endemic had vigorous proliferation responses to one or more of the LSA1 peptides (mean stimulation indices of 6.8 to 7.2). Gamma interferon (IFN-gamma) production driven by LSA1 peptides ranged from 34 to more than 3,500 pg/2 x 10(6) cells, was derived primarily from CD8+ cells, and was dissociated from T-cell proliferation. The frequencies of IFN-gamma response to the amino acid 1819 to 1835 and 1888 to 1909 peptides were significantly greater than that to the amino acid 84 to 107 peptide (87 and 88% versus 33% of subjects; P < 0.0001). In contrast to proliferation and IFN-gamma, interleukin 4 (IL-4) and/or IL-5 responses to LSA1 peptides were detected in only 18% of the subjects. These data show that T-cell immunity to epitopes in the N- and C-terminal regions of LSA1 are common in persons living in this area of Papua New Guinea where malaria is endemic. The dominance of type 1 CD8 cell IFN-gamma responses is consistent with a role for this T-cell population in immunity to liver-stage Plasmodium falciparum in humans.
肝期抗原1（LSA1）是几种被考虑纳入针对恶性疟原虫的多抗原、多阶段亚单位疫苗的红细胞前期抗原之一。我们检测了生活在疟疾高度流行的巴布亚新几内亚某地区的无症状成年人对与LSA1的第84至107位、1813至1835位和1888至1909位氨基酸对应的肽段的T细胞增殖和细胞因子反应。从未接触过疟疾的北美人群的T细胞对任何肽段均无反应，而来自该疟疾流行地区的55名成年人中的52人的T细胞对一种或多种LSA1肽段有强烈的增殖反应（平均刺激指数为6.8至7.2）。由LSA1肽段驱动的γ干扰素（IFN-γ）产生量在34至超过3500 pg/2×10⁶个细胞之间，主要来源于CD8⁺细胞，且与T细胞增殖无关。对第1819至1835位和1888至1909位氨基酸肽段的IFN-γ反应频率显著高于对第84至107位氨基酸肽段的反应频率（分别为87%和88%的受试者，而对第84至107位氨基酸肽段有反应的受试者为33%；P<0.0001）。与增殖和IFN-γ不同，仅在18%的受试者中检测到对LSA1肽段的白细胞介素4（IL-4）和/或IL-5反应。这些数据表明，在疟疾流行的巴布亚新几内亚该地区生活的人群中，对LSA1 N端和C端区域表位的T细胞免疫很常见。1型CD8细胞IFN-γ反应的主导地位与该T细胞群体在人类对恶性疟原虫肝期免疫中的作用一致。
