Frontline: Multispecific responses by T cells expanded by endogenous self-peptide/MHC complexes
Frontline: Multispecific responses by T cells expanded by endogenous self-peptide/MHC complexes
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DOI：
10.1002/eji.200636787
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发表时间：
2007-03-01
影响因子：
5.4
通讯作者：
Hafler, David A.
中科院分区：
文献类型：
--
作者：
Cai, Guifang;Hafler, David A.
生理性免疫应答与病理性免疫应答相对的自身肽的自身反应性的矛盾尚未得到很好的理解。在这里，我们直接检查了一系列健康受试者的人T细胞对内源性自身肽的反应。用含有内源性自身抗原的未操作的抗原呈递细胞刺激CFSE标记的T细胞，并对进入细胞周期的所得CD 4（+）群体（CFSE低）或非增殖CD 4（+）细胞（CFSE高）进行单细胞分选、克隆并针对一组自身抗原和微生物回忆抗原进行筛选，以询问其抗原反应性。CD 4 + T细胞在自身肽/MHC刺激下进入细胞周期的百分率为0.04%，进入细胞周期依赖于CD 28的共刺激。与微生物抗原刺激后产生的CFSEhigh克隆或其他CD 4（+）克隆相比，源自CFSElow T细胞的克隆对多种抗原表现出显著更大的交叉反应性。对TCRP链进行测序表明CFSE低克隆确实是克隆的。这些数据表明，由内源性自身肽刺激产生的T细胞克隆表现出高度的多特异性，我们推测，它们的多特异性是基于共享的骨架MHC决定簇的识别。
The paradox of autoreactivity to self-peptides in physiological as opposed to pathological immune responses is not well understood. Here, we directly examined the human T cell response to endogenous self-peptides in a series of healthy subjects. CFSE-labeled T cells were stimulated with unmanipulated antigen-presenting cells containing endogenous self-antigen, and the resulting CD4(+) populations entering into cell cycle (CFSElow) or non-proliferating CD4(+) cells (CFSEhigh) were single-cell sorted, cloned and screened against a panel of self-antigens and microbial recall antigens to interrogate their antigen reactivity. The percentage of CD4(+) T cells entering cell cycle in response to self-peptide/MHC was calculated to be 0.04%, and entry into cell cycle was dependent upon CD28 costimulation. Clones derived from CFSElow T cells exhibited significantly greater cross-reactivity to multiple antigens than CFSEhigh clones or other CD4(+) clones generated after microbial antigen stimulation. Sequencing the TCRP chains indicated that CFSElow clones were indeed clonal. These data demonstrate that T cell clones generated on stimulation by endogenous self-peptides exhibit a high degree of multispecificity, and we speculate that their multispecificity is based upon recognition of shared-backbone MHC determinants.