Fell A H, Silins S L, Baumgarth N, Good M F
Malaria and Arbovirus Unit, Queensland Institute of Medical Research, Royal Brisbane Hospital, Australia.
Int Immunol. 1996 Dec;8(12):1877-87. doi: 10.1093/intimm/8.12.1877.
Humans lacking previous exposure to Plasmodium falciparum typically have a high frequency of malaria-reactive T cells in peripheral blood, which cross-react with antigens from other microorganisms. We studied a large number of malaria-specific human T cell clones from non-exposed and malaria-exposed donors to determine whether this response is oligoclonal, and might therefore be generated by a limited number of cross-reactive epitopes. Most clones responded well to schizont antigen from three antigenically distinct stocks of P. falciparum. Clones derived from the same donor tended to show similar patterns of reactivity to a panel of non-malaria antigens from various microorganisms, suggesting that a limited number of epitopes were recognized by individuals. However, analysis of the usage of V segments of the beta chain of the TCR (TCRBV) revealed no evidence of TCRBV restriction in the T cell response, either within individual donors or across all donors. An apparent skewing towards TCRBV8 in one donor was shown by two methods to be due to in vitro expansion of a single clone: (i) Direct sorting of TCRBV8+ CD4+ T cells from fresh PBMC did not reveal any enrichment for pRBC-reactive cells; (ii) Sequencing of VDJ regions revealed that the TCRBV8 clones were identical. Sequences of non-TCRBV8 clones from this donor showed major differences in the VDJ junctional region. No differences in TCRBV repertoire between non-exposed and exposed donors were observed. These results exclude the existence of a malarial superantigen and suggest that the T cell response to malaria schizont antigen in non-exposed donors is driven by a large number of epitopes.
以前未接触过恶性疟原虫的人外周血中通常有高频率的疟疾反应性T细胞，这些T细胞会与来自其他微生物的抗原发生交叉反应。我们研究了大量来自未接触疟疾和接触过疟疾的供体的疟疾特异性人类T细胞克隆，以确定这种反应是否为寡克隆性的，因此是否可能由有限数量的交叉反应表位产生。大多数克隆对来自三种抗原性不同的恶性疟原虫毒株的裂殖体抗原有良好反应。来自同一供体的克隆对来自各种微生物的一组非疟疾抗原往往表现出相似的反应模式，这表明个体识别的表位数量有限。然而，对TCR（TCRBV）β链V区使用情况的分析表明，无论是在个体供体内还是所有供体中，T细胞反应中都没有TCRBV限制的证据。通过两种方法表明，一名供体中明显偏向TCRBV8是由于单个克隆的体外扩增：（i）从新鲜PBMC中直接分选TCRBV8+CD4+T细胞未发现对pRBC反应性细胞有任何富集；（ii）VDJ区域测序显示TCRBV8克隆是相同的。该供体的非TCRBV8克隆序列在VDJ连接区显示出主要差异。未接触和接触过疟疾的供体之间在TCRBV库方面未观察到差异。这些结果排除了疟疾超抗原的存在，并表明未接触疟疾的供体中对疟疾裂殖体抗原的T细胞反应是由大量表位驱动的。
