MHC class II tetramers identify peptide-specific human CD4+ T cells proliferating in response to influenza A antigen
MHC class II tetramers identify peptide-specific human CD4+ T cells proliferating in response to influenza A antigen
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DOI：
10.1172/jci8476
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发表时间：
1999-12-01
影响因子：
15.9
通讯作者：
Kwok, WW
中科院分区：
文献类型：
--
作者：
Novak, EJ;Liu, AW;Kwok, WW
以非常低的频率存在于外周血中的抗原特异性T辅助细胞能够在抗原攻击期间快速克隆扩增。这种反应的精致特异性提供了非常选择的T细胞群的激活和扩增，我们已经使用该特征来直接鉴定和定量来自外周血的人表位特异性T辅助细胞。可溶性四聚化II类MHC分子，装载有来自血凝素（HA）的免疫显性肽并用荧光染料标记，构建并用于直接鉴定来自流感免疫个体的抗原特异性T细胞。在响应于HA肽或完整流感疫苗的刺激而增殖7天后，用HA四聚体染色阳性的细胞经历了6至9次分裂，并且是CD 3（+）、CD 4（+）、CD 25（+）和CD 8（-），这是响应于抗原的活化T辅助细胞的特征。HA表位特异性组分的复杂反应，整个流感疫苗代表了一个主要的子集的增殖T辅助细胞。可溶性II类四聚体允许用于分析免疫显性抗原特异性的直接方法。外周血中抗原特异性T辅助细胞的鉴定提供了用于追踪针对感染因子和自身免疫性疾病的免疫应答的手段。
Antigen-specific T helper cells present in peripheral blood at very low frequencies are capable of rapid clonal expansion during antigenic challenge. The exquisite specificity of this response provides for activation and expansion of a very select cohort of T cells, a feature we have used to directly identify and quantify human epitope-specific T helper cells from peripheral blood Soluble tetramerized class II MHC molecules, loaded with an immunodominant peptide from hemagglutinin (HA) and labeled with fluorescent dyes, were constructed and used to directly identify antigen-specific T cells from influenza-immune individuals. After 7 days of proliferation in response to stimulation by HA peptide or whole influenza vaccine, cells staining positive with the HA tetramer had undergone between 6 and 9 divisions and were CD3(+), CD4(+), CD25(+), and CD8(-), characteristic of activated T helper cells responding to antigen. The HA epitope-specific component of the complex response to whole influenza vaccine represented a major subset of proliferating T helper cells. Soluble class II tetramers allow a direct approach for the analysis of immunodominant antigenic specificities. The identification of antigen-specific T helper cells in the peripheral blood provides a means for tracking the immune response against infectious agents and in autoimmune disease.