T CELL RESPONSE TO MBP--REPERTOIRE/DOMINANCE/SUPPRESSION

比较MBP和MBP多肽对T细胞的诱导作用。就这样， 每种菌株中的主要决定因素都能激活反应， 当MBP是免疫原时，就会被学习。将提高T细胞克隆 以适当的决定因素来完成另一个特定的 目标。这些克隆对II类MHC蛋白的特异性将是 研究，克隆将被用来确定 将对蛋白质进行研究，并将使用克隆来确定 部分MBP决定簇与第II类MHC抗原结合 演示文稿。利用显性和亚显性的嵌合肽 决定因素将被用来研究负责 免疫优势等级。T细胞谱系的可塑性将 通过研究亲本-F1嵌合体(C57L-(B10.PL x))进行检验 C57BL/6)F1)；(SJL-(B10.PL x SJL)F1)，其中每个捐赠者都有 基因截短的曲目缺失了几个V-β基因。在MBP中 B10.PL小鼠对优势氨基末端决定簇的反应 用于T细胞反应的V-β基因受到高度限制。这些V- C57L和SJL小鼠中缺失β基因：问题是 C57L和C57L截短谱系中V-β基因的剩余部分 SJL动物足以产生反应吗？T细胞克隆的诱导 对主要和次要多肽的失活耐受性(或 脑性或非脑性)将在第3章中研究 菌株，特别是确定对反应的影响和 诱发MBP的疾病。此外，我们将尝试诱导 在出生或成年时对MBP的耐受性，并决定耐受性 只诱导出显性决定因素。T抑制细胞诱导 MBP上的决定因素(SD)将被鉴定，SD上的溶菌酶将是 “嫁接”到能够诱导EAE的MBP多肽上，以努力 阻止T细胞对后一种多肽的反应。它的特殊性 克隆“疫苗”实验将在3个品系的小鼠身上进行研究。 在体外也是如此。这种疫苗接种提供的保护是 归因于独特型特定的交互作用，我们将尝试 确定识别的独特型是否与特定的T细胞有关 识别抗原或MHC的独特型结构。

T cell induction by MBP and MBP peptides will be compared. In this way, the dominant determinants sin each strain that can activate responses, when MBP is the immunogen, will be learned. T cell clones will be raised to suitable determinants to be used to accomplish the other specific aims. The specificity of these clones for Class II MHC proteins will be studied, and the clones will be used to establish which portions of proteins will be studied, and the clones will be used to establish which portions of MBP determinants bind to Class II MHC in antigen presentation. Chimeric peptides employing dominant and subdominant determinants will be used to study mechanisms responsible for immunodominance hierarchies. The plasticity of the T cell repertoire will be examined by studying parent-- F1 chimeras (C57L-- (B10.PL x C57BL/6)F1); (SJL- (B10.PL x SJL)F1) in which each of these donors has a genetically truncated repertoire missing several V-beta genes. In the MBP response to the dominant, aminoterminal determinant in B10.PL mice, the V-beta genes used in the T cell response are highly restricted. These V- beta genes are missing in C57L and SJL mice: the question is whether the remainder of the V-beta genes in the truncated repertoires of C57L and SJL animals suffice to produce a response? The induction of T cell clonal inactivation tolerance to both dominant and subdominant peptides (either encephalitogenic or non encephalitogenic) will be studied in the 3 strains, in particular to determine the effect on the response and induction of disease to MBP. Furthermore, we will attempt to induce tolerance to MBP at birth or in adulthood and determine whether tolerance is only induced to dominant determinants. T suppressor cell-inducing determinants (SD) on MBP will be identified SD on lysozyme will be "grafted" onto MBP peptides capable of inducing EAE in an effort to prevent the T cell response to the latter peptides. The specificity of clonal "vaccination" experiments will be studied in the 3 mouse strains as well as in vitro. The protection afforded by this vaccination has been attributed to idiotype-specific interactions and we will attempt to define whether the idiotypes recognized are related to specific T cell idiotypic structure for antigen or MHC recognition.