Gold D P, Vainiene M, Celnik B, Wiley S, Gibbs C, Hashim G A, Vandenbark A A, Offner H
La Jolla Institute for Experimental Medicine, CA 92037.
J Immunol. 1992 Mar 15;148(6):1712-7.
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.
在实验性变应性脑脊髓炎中，Lewis大鼠淋巴结T细胞对豚鼠髓鞘碱性蛋白（GP - BP）的免疫反应主要针对由第72 - 89位氨基酸残基所包围的碱性蛋白区域。对该表位产生反应的T细胞受主要组织相容性复合体（MHC）的RT1.B II类分子限制，并且在其T细胞受体（TCR）中仅使用Vβ8.2。GP - BP的第二个区域，即第87 - 99位氨基酸残基，在Lewis大鼠中也可诱导实验性变应性脑脊髓炎，但这种反应主要受RT1.D限制。在其他地方，我们描述了对合成肽s87 - 99以及相关肽s85 - 99产生反应的T细胞克隆的生物学特性。我们对这些克隆中TCR Vβ基因表达进行了详细分析，这些克隆来源于免疫动物的淋巴结和脊髓，以及对GP - BP 72 - 89产生反应的脊髓来源的T细胞克隆。我们发现，对s85 - 99和s87 - 99产生反应的脊髓来源克隆主要使用Vβ6。相反，来源于淋巴结且对相同肽产生反应的T细胞克隆表达多种Vβ基因，包括Vβ6。在来源于脊髓和免疫淋巴结的T细胞系中也可见到克隆水平上Vβ使用异质性的这种差异。对Vβ6 +脊髓克隆中CDR3区域的DNA序列比较显示，在脊髓抗s85 - 99细胞系的大多数Vβ6序列中也发现了一个保守的氨基酸基序。尽管Vβ6在一些来源于淋巴结的克隆中表达，但只有一个克隆含有与脊髓分离株中所见相似的CDR3区域。所有对GP - BP 72 - 89产生反应的脊髓来源T细胞克隆都使用Vβ8.2，并且大多数（六个中的五个）在CDR3中含有天冬氨酸 - 丝氨酸残基，先前已表明这些残基与大多数对GP - BP 72 - 89产生反应的淋巴结T细胞所表达的Vβ8.2受体相关。这些数据表明，对外源性自身抗原产生反应的外周T细胞中TCR Vβ的使用情况并不总是能够预测自身免疫攻击部位T细胞中的Vβ使用情况。本文讨论了在来源于脊髓的T细胞克隆中所见TCR Vβ表达相对同质性的可能解释。
