根据2012年2月6日在线发表在Journal of Experimental Medicine期刊上的一篇研究论文，能够攻击健康器官的免疫细胞“观察”它们的靶标不同于攻击病毒的保护性免疫细胞。
在发育期间，身体安全筛查能够识别攻击正常组织的T淋巴细胞。这些自身反应性T细胞(autoreactive T cell)通常被清除掉，但是也有一些细胞从这些防御体系中溜掉，从而可能造成自身免疫疾病。
来自美国达纳法伯癌症研究所(Dana-Farber Cancer Institute)和哈佛医学院的Kai Wucherpfennig发现来自多发性硬化症和I型糖尿病病人的自身反应性T细胞要比检测流感病毒的有益性T细胞更差地结合它们的靶标。一旦遭遇到流感病毒，对该病毒作出反应的T细胞停止流动，重新定位它们的识别装置(recognition machinery)到靶细胞上。相反，自身反应性T细胞似乎发生错乱从而越过它们的预定目标。
这些结果提示着一些自身攻击性T细胞(autoaggressive T cell)可能只是因为不能识别它们的靶标而逃过发育安全筛查。(生物谷：towersimper编译)
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.
