Naturally Presented Peptides on Major Histocompatibility Complex I and II Molecules Eluted from Central Nervous System of Multiple Sclerosis Patients
Naturally Presented Peptides on Major Histocompatibility Complex I and II Molecules Eluted from Central Nervous System of Multiple Sclerosis Patients
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DOI：
10.1074/mcp.m900001-mcp200
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发表时间：
2009-09-01
影响因子：
7
通讯作者：
Weissert, Robert
中科院分区：
文献类型：
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作者：
Fissolo, Nicolas;Haag, Sabrina;Weissert, Robert
用串联质谱仪鉴定了8例多发性硬化(MS)患者中枢神经系统(CNS)中主要组织相容性复合体(MHC)I和MHC II分子的天然加工多肽。用针对人类白细胞抗原-A、-B、-C和-DR的单抗进行免疫亲和层析，从尸检的中枢神经系统材料中纯化MHC分子。随后用反相高效液相色谱分离多肽，并用质谱仪进行分析。数据库搜索显示，来自MHC I分子洗脱的自身蛋白质的118个氨基酸序列和来自MHC II分子的191个氨基酸序列，对应于174个已识别的源蛋白质。这些序列定义了多发性硬化症中已知的和潜在的新的自身抗原，可能参与疾病的诱导和抗原的传播。综上所述，我们已经启动了中枢神经系统疾病中表达的MHC配子组的特征，并能够展示自然加工的髓鞘碱性蛋白多肽在MS患者脑中的存在。《分子与细胞蛋白质组学》8：2090-2101,2009。
Tandem mass spectrometry was used to identify naturally processed peptides bound to major histocompatibility complex (MHC) I and MHC II molecules in central nervous system (CNS) of eight patients with multiple sclerosis (MS). MHC molecules were purified from autopsy CNS material by immunoaffinity chromatography with monoclonal antibody directed against HLA-A, -B, -C, and -DR. Subsequently peptides were separated by reversed-phase HPLC and analyzed by mass spectrometry. Database searches revealed 118 amino acid sequences from self-proteins eluted from MHC I molecules and 191 from MHC II molecules, corresponding to 174 identified source proteins. These sequences define previously known and potentially novel autoantigens in MS possibly involved in disease induction and antigen spreading. Taken together, we have initiated the characterization of the CNS-expressed MHC ligandome in CNS diseases and were able to demonstrate the presentation of naturally processed myelin basic protein peptides in the brain of MS patients. Molecular & Cellular Proteomics 8: 2090-2101, 2009.