Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells.
Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells.
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DOI：
10.4049/jimmunol.148.6.1712
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发表时间：
1992-03
影响因子：
4.4
通讯作者：
D. Gold;M. Vainiene;B. Celnik;S. Wiley;C. Gibbs;G. Hashim;A. Vandenbark;H. Offner
中科院分区：
文献类型：
--
作者：
D. Gold;M. Vainiene;B. Celnik;S. Wiley;C. Gibbs;G. Hashim;A. Vandenbark;H. Offner
实验性变态反应性脑脊髓炎中刘易斯大鼠淋巴结T细胞对豚鼠髓鞘碱性蛋白（GP-BP）的免疫应答主要针对由残基72-89所包含的碱性蛋白区域。响应于该表位的T细胞受到MHC的RT1.B II类分子的限制，并且仅在其TCR中使用V β 8.2。GP-BP的第二个区域，残基87-99，也诱导刘易斯大鼠的实验性过敏性脑脊髓炎，但这种反应主要受RT1.D的限制。在其他地方，我们描述了T细胞克隆的生物学特性的合成肽，S87-99，和相关的肽，S85-99。我们提出了一个详细的分析TCR V β基因表达这些克隆，来自免疫动物的淋巴结和脊髓，和脊髓衍生的T细胞克隆GP-BP 72-89反应。我们发现，脊髓衍生的克隆，反应s85-99和s87-99，主要使用V β 6。相反，来自淋巴结并对相同肽反应的T细胞克隆表达多个V β基因，包括V β 6。在克隆水平上V β使用的异质性的这种差异也见于来源于脊髓和免疫淋巴结的T细胞系中。V β 6+脊髓克隆中CDR 3区域的DNA序列比较揭示了在脊髓抗s85 -99系的大多数V β 6序列中也发现的保守氨基酸基序。虽然V β 6在一些淋巴结来源的克隆中表达，但只有一个克隆含有与脊髓分离物中所见相似的CDR 3区域。所有对GP-BP 72-89有反应性的脊髓来源的T细胞克隆都使用V β 8.2，并且大多数（6个中的5个）含有先前显示与大多数对GP-BP 72-89有反应的淋巴结T细胞表达的V β 8.2受体相关的CDR 3中的AspSer残基。这些数据表明，响应于自身抗原的外周T细胞中的TCR V β使用并不总是预测自身免疫攻击位点处的T细胞中的V β使用。可能的appropritations的相对同质性TCR V β表达中看到的T细胞克隆来自脊髓进行了讨论。
The immune response of Lewis rat lymph node T cells to guinea pig myelin basic protein (GP-BP) in experimental allergic encephalomyelitis is directed primarily against a region of basic protein encompassed by residues 72-89. T cells that respond to this epitope are restricted by the RT1.B class II molecule of the MHC and use V beta 8.2 exclusively in their TCR. A second region of GP-BP, residues 87-99, also induces experimental allergic encephalomyelitis in Lewis rats but this response is restricted primarily by RT1.D. Elsewhere we describe the biologic characteristics of T cell clones responding to the synthetic peptide, s87-99, and to a related peptide, s85-99. We present a detailed analysis of TCR V beta gene expression among these clones, derived from the lymph node and spinal cord of immunized animals, and among spinal cord derived T cell clones reactive to GP-BP 72-89. We find that spinal cord-derived clones, reactive to s85-99 and to s87-99, use V beta 6 predominantly. In contrast, T cell clones derived from lymph nodes and reactive to the same peptides express multiple V beta genes including V beta 6. This difference in heterogeneity of V beta usage at the clonal level is also seen in T cell lines derived from spinal cord and immune lymph node. DNA sequence comparison of the CDR3 regions in V beta 6+ spinal cord clones revealed a conserved amino acid motif also found in the majority of V beta 6 sequences from the spinal cord anti-s85-99 line. Although V beta 6 was expressed in some lymph node-derived clones, only one contained a CDR3 region similar to that seen in spinal cord isolates. All spinal cord-derived T cell clones reactive to GP-BP 72-89 used V beta 8.2 and most (five of six) contained the AspSer residues in CDR3 previously shown to be associated with V beta 8.2 receptors expressed by the majority of lymph node T cells responding to GP-BP 72-89. These data indicate that TCR V beta usage in peripheral T cells responding to an autoantigen does not always predict the V beta usage among T cells at the site of an autoimmune attack. Possible explantations for the relative homogeneity in TCR V beta expression seen in T cell clones derived from the spinal cord are discussed.