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

将比较MBP和MBP肽的T细胞诱导。通过这种方式， 每个菌株中能激活反应的主要决定因素， 当MBP是免疫原时，将被学习。T细胞克隆将被培养 到合适的决定因素被用来完成其他具体的 目标。这些克隆对II类MHC蛋白的特异性将是 研究，克隆将被用来建立哪些部分的 蛋白质将被研究，克隆将被用来建立 MBP决定簇的一部分与抗原中的II类MHC结合 演示文稿.使用显性和次显性的嵌合肽 决定因素将被用来研究机制负责 免疫优势等级T细胞库的可塑性将 通过研究亲本- F1嵌合体（C57 L-（B10.PLx C57 BL/6）F1）;（SJL-（B10.PLx SJL）F1），其中这些供体中的每一个具有 缺失了几个V-β基因的基因截短的库。在MBP中 在B10.PL小鼠中， 用于T细胞应答的V-β基因受到高度限制。这些V- β基因在C57 L和SJL小鼠中缺失：问题是 C57 L的截短谱系中的V-β基因的剩余部分， SJL动物足以产生反应？T细胞克隆的诱导 对显性和次显性肽的失活耐受性（或者 致脑炎性或非致脑炎性）将在3 菌株，特别是确定对反应的影响， 疾病对MBP的诱导。此外，我们将尝试诱导 在出生或成年时对MBP的耐受性，并确定耐受性是否 只会导致显性决定因素。T抑制细胞诱导 将确定MBP的决定因素（SD），将确定溶菌酶的SD， “嫁接”到能够诱导EAE的MBP肽上， 阻止T细胞对后一种肽的应答。的特异性 将在3个小鼠品系中研究克隆“接种”实验 以及在体外。这种疫苗提供的保护， 归因于白痴特异性相互作用，我们将尝试 确定识别的独特型是否与特定的T细胞相关， 抗原或MHC识别的独特型结构。

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.