De Groot Anne S, Goldberg Miriam, Moise Leonard, Martin William
EpiVax, Inc., Providence, RI 02903, USA.
Cell Immunol. 2006 Dec;244(2):148-53. doi: 10.1016/j.cellimm.2007.02.006. Epub 2007 Apr 18.
Self-proteins in the extracellular environment are constantly sampled and processed through the Class II antigen presentation pathway. Mechanisms responsible for central and peripheral tolerance reduce the chance of autoimmune responses to these proteins. However, tolerance can and does break down, leading to the development of autoimmune disease. In a preliminary analysis, we observed that common serum proteins have fewer HLA class II-restricted T-cell epitopes than expected, when compared to random protein sequences. We therefore performed a broader analysis of human proteins to determine whether the number of T-cell epitopes in extracellular proteins is reduced in comparison with non-secreted (intracellular) proteins. Here we document fewer putative HLA class II-restricted T-cell epitopes in extracellular proteins, compared to intracellular proteins. These data suggest that the diminished presence of T-cell epitopes may reduce the potential for autoimmunity. Over evolutionary timescales, immune pressure may have resulted in alterations in the inherent T-cell immunogenic potential of autologous proteins.
细胞外环境中的自身蛋白不断通过II类抗原呈递途径进行取样和加工。负责中枢和外周耐受的机制降低了对这些蛋白产生自身免疫反应的可能性。然而，耐受可能而且确实会被打破，从而导致自身免疫性疾病的发生。在初步分析中，我们观察到，与随机蛋白质序列相比，常见血清蛋白的HLA II类限制性T细胞表位比预期的要少。因此，我们对人类蛋白质进行了更广泛的分析，以确定细胞外蛋白中的T细胞表位数量与非分泌（细胞内）蛋白相比是否减少。在此我们记录到，与细胞内蛋白相比，细胞外蛋白中推定的HLA II类限制性T细胞表位较少。这些数据表明，T细胞表位的减少可能会降低自身免疫的可能性。在进化时间尺度上，免疫压力可能导致了自体蛋白固有T细胞免疫原性潜力的改变。
