Enders Matthias H, Bayarsaikhan Ganchimeg, Ghilas Sonia, Chua Yu Cheng, May Rose, de Menezes Maria N, Ge Zhengyu, Tan Peck Szee, Cozijnsen Anton, Mollard Vanessa, Yui Katsuyuki, McFadden Geoffrey I, Lahoud Mireille H, Caminschi Irina, Purcell Anthony W, Schittenhelm Ralf B, Beattie Lynette, Heath William R, Fernandez-Ruiz Daniel
Dept. of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, 3000, Australia.
The ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, 3010, Australia.
Curr Res Immunol. 2021 Jun 30;2:79-92. doi: 10.1016/j.crimmu.2021.06.002. eCollection 2021.
Thorough understanding of the role of CD4 T cells in immunity can be greatly assisted by the study of responses to defined specificities. This requires knowledge of -derived immunogenic epitopes, of which only a few have been identified, especially for the mouse C57BL/6 background. We recently developed a TCR transgenic mouse line, termed PbT-II, that produces CD4 T cells specific for an MHC class II (I-A)-restricted epitope and is responsive to both sporozoites and blood-stage . Here, we identify a peptide within the heat shock protein 90 as the cognate epitope recognised by PbT-II cells. We show that C57BL/6 mice infected with blood-stage induce an endogenous CD4 T cell response specific for this epitope, indicating cells of similar specificity to PbT-II cells are present in the naïve repertoire. Adoptive transfer of activated T1-, or particularly T2-polarised PbT-II cells improved control of parasitemia in C57BL/6 mice and drastically reduced the onset of experimental cerebral malaria. Our results identify a versatile, potentially protective MHC-II restricted epitope useful for exploration of CD4 T cell-mediated immunity and vaccination strategies against malaria.
对特定特异性反应的研究能够极大地帮助深入理解CD4 T细胞在免疫中的作用。这需要了解源自疟原虫的免疫原性表位，然而目前仅鉴定出少数此类表位，尤其是针对小鼠C57BL/6背景的表位。我们最近开发了一种TCR转基因小鼠品系，称为PbT-II，它能产生针对MHC II类（I-A）限制性疟原虫表位的CD4 T细胞，并且对子孢子和血液期疟原虫均有反应。在此，我们确定热休克蛋白90内的一种肽段为PbT-II细胞识别的同源表位。我们发现，感染血液期疟原虫的C57BL/6小鼠会诱导出针对该表位的内源性CD4 T细胞反应，这表明在未感染的小鼠体内存在与PbT-II细胞具有相似特异性的细胞。过继转移活化的T1或特别是T2极化的PbT-II细胞可改善C57BL/6小鼠对疟原虫血症的控制，并显著减少实验性脑型疟疾的发作。我们的研究结果确定了一种通用的、可能具有保护作用的MHC-II限制性表位，有助于探索CD4 T细胞介导的免疫以及针对疟疾的疫苗接种策略。
