根據2012年2月6日在線發(fā)表在Journal of Experimental Medicine期刊上的一篇研究論文，能夠攻擊健康器官的免疫細胞“觀察”它們的靶標不同于攻擊病毒的保護性免疫細胞,。
在發(fā)育期間,，身體安全篩查能夠識別攻擊正常組織的T淋巴細胞。這些自身反應性T細胞(autoreactive T cell)通常被清除掉,，但是也有一些細胞從這些防御體系中溜掉,，從而可能造成自身免疫疾病。
來自美國達納法伯癌癥研究所(Dana-Farber Cancer Institute)和哈佛醫(yī)學院的Kai Wucherpfennig發(fā)現來自多發(fā)性硬化癥和I型糖尿病病人的自身反應性T細胞要比檢測流感病毒的有益性T細胞更差地結合它們的靶標,。一旦遭遇到流感病毒,，對該病毒作出反應的T細胞停止流動，重新定位它們的識別裝置(recognition machinery)到靶細胞上,。相反,，自身反應性T細胞似乎發(fā)生錯亂從而越過它們的預定目標。
這些結果提示著一些自身攻擊性T細胞(autoaggressive T cell)可能只是因為不能識別它們的靶標而逃過發(fā)育安全篩查,。(生物谷：towersimper編譯)
doi:10.1084/jem.20111485
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Self-reactive human CD4 T cell clones form unusual immunological synapses
David A. Schubert1, Susana Gordo1, Joseph J. Sabatino Jr.3, Santosh Vardhana4,5, Etienne Gagnon1, Dhruv K. Sethi1, Nilufer P. Seth1, Kaushik Choudhuri4,5, Helena Reijonen6, Gerald T. Nepom6, Brian D. Evavold3, Michael L. Dustin4,5, and Kai W. Wucherpfennig
Recognition of self–peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR–pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease.
