T CELL RESPONSE TO MEP-REPERTOIRE AND REGULATION

有许多调节和诱导的影响， 对自身抗原如髓磷脂碱性蛋白的应答的传播 （MBP）。抗原的形式，抗原呈递细胞的性质， 在仔细检查下的T细胞库中的耐受性水平，以及 基于抗原和基于T细胞受体（TCR）的调节因子的成员 电路都直接参与其中。这些影响的各个方面 表达T细胞库MBP和点，另一个神经元 蛋白质，蛋白脂质蛋白（=PLP），将被研究。调节电路 由CD 4 + T调节细胞（抑制子诱导的细胞）和CD 4 + T调节细胞组成。 CD 8 + T抑制细胞已在我们的实验室中描述，其作用是 控制负责疾病的CD 4+效应T细胞的活性。 在这项提案中，目标之一将是研究CD 8 + T细胞的作用， 这个回路中的细胞--它的特异性和调节目标。TCR 转基因系统将采用低频率的T细胞 携带转基因受体。同样，监管可以由以下方面启动： 抗原，虽然它也继续从事TCR的独特肽为基础的 电路，我们想研究T抑制细胞诱导的 MBP上的抑制性T细胞诱导决定簇。我们将调查 抗原决定簇的存在形式 以及所选T细胞的TCR中V基因的使用。两种类型的 将进行耐受性试验。其中之一的重点是 自身蛋白质MBP上的次显性和隐性决定簇及其 重要性在延续神经系统疾病，实验性过敏 脑脊髓炎此外，肽在诱导免疫应答中的有效性是显著的。 将测试疾病慢性期的耐受性。我们将探讨 肽配体对MHC分子亲和力的变化如何 影响T细胞成熟的方向， Th 1/Th 2细胞在抗原刺激后产生。这些研究 应该有助于建立一个更清晰的理解和潜在的治疗方法， 治疗这种自身免疫性疾病

There are many regulatory and inductive influences on the generation and propagation of response to a self-antigen such as myelin basic protein (MBP). The form of the antigen, the nature of the antigen-presenting cell, the level of tolerance in the T cell repertoire under scrutiny, and members of antigen-based and T cell receptor (TCR)-based regulatory circuits are all directly involved. Aspects of these influences on the expressed T cell repertoire to MBP and at points, to another neuronal protein, proteolipid protein (=PLP), will be studied. A regulatory circuit comprised of a CD4+ T regulatory cell (a suppressor-induced cell) and a CD8+ T suppressor cell has been described in our laboratory, which acts to control the activity of the CD4+ effector T cells responsible for disease. In this proposal, one of the aims will be to study the role of the CD8+ T cell in this circuit--its specificity and regulatory target. TCR transgenic systems will be employed with low frequencies of T cells bearing the transgenic receptor. Likewise, regulation can be initiated by antigen, and although it also proceeds to engage the TCR idiopeptide-based circuit, we would like to study the T suppressor cell induced by suppressor T cell-inducing determinants on MBP. We will investigate the relationship between the form in which the antigenic determinant exists and the V gene usage in the TCR of the selected T cells. Two types of tolerance experiments will be undertaken. One of them has as its focus the subdominant and cryptic determinants on the self protein, MBP, and their importance in perpetuating the neurologic disease, experimental allergic encephalomyelitis. Further, the effectiveness of peptides in inducing tolerance during chronic phases of disease will be tested. We will explore how a change in the affinity of peptide ligands for the MHC molecule can affect the direction of T cell maturation and influence the proportion of Th1 of Th2 cells produced after antigenic stimulation. These studies should help to establish a clearer understanding and potential therapies for this autoimmune disease.