POLYMORPHISM WITHIN T4/LEU3 AND SLE

T4/Leu3分子是一种T细胞分化抗原，已被 被证明有助于B细胞分化，与II类主要细胞相互作用 非T细胞上的组织相容性(MHC)抗原，并形成部分 HTLV-III病毒的受体复合体。尽管最初认为 是单态的，这种分子最近被证明表现出有限的 多态。假设T细胞的细胞功能是 依赖于表达的T4/Leu3表型。三个具体目标将是 地址。1)T4/Leu3基因的多态性特征。 小鼠免疫后可产生单抗。 来自已知表位差异的个体的T细胞 单抗OKT4(T4表位)。预计其中一些单抗将 识别其他多态表位，并将用于筛选不同的 用于表达给定表位的个体。2)体外评价 通过表达不同T4/Leu3表型的T细胞发挥作用。T细胞 表达不同T4/Leu3表型的人将接受帮助和测试 B细胞分化和增殖的抑制反应 召回抗原、有丝分裂原、自体和同种异体MHC抗原。 使用针对不同表位的单抗进行阻断实验将是 以测试T4/Leu3分子的不同部分是否发挥作用 不同职能的重要角色。除了测试 T4/Leu3-II类MHC抗原相互作用及单抗对类的影响 将评估II MHC抗原并将其与T4/Leu3表型相关联。3) T4Leu3表型与系统性红斑狼疮易感性的关系 红斑狼疮(SLE)。初步研究表明， T4表位缺失与SLE的发生发展。正常人，红斑狼疮 患者和非风湿性疾病的患者将被筛查 T4/Leu3表型来证实这些最初的观察结果并相互关联 具有临床和血清学表现的T4/Leu3表型。

The T 4/Leu3 moleculeis a T cell differentiation antigen which has been shown to help in B cell differentiation, to interact with class II major histocompatibility (MHC) antigens on non-T cells, and to form part of the receptor complex for the HTLV-III virus. Although originally believed to be monomorphic, this molecule has recently been shown to manifest a limited polymorphism. It is hypothesized that the cellular function of T cells is dependent on the T4/Leu3 phenotype expressed. Three specific aims will be addressed. 1) Characterization of the polymorphism within T4/Leu3. Monoclonal antibodies (mAb) will be generated from mice by immunizing with T cells from individuals with known differences at the epitope recognized by mAb OKT4 (T4 epitope). It is anticipated that some of these mAb will recognize other polymorphic epitopes and will be used to screen different individuals for expression of the given epitope. 2) Assessment of in vitro function by T cells expressing different T4/Leu3 phenotypes. T cells expressing different T4/Leu3 phenotypes will be tested for help and suppression in B cell differentiation as well as proliferation in response to recall antigens, mitogens, and autologous and allogeneic MHC antigens. Blocking experiments using mAb directed against different epitopes will be performed to test whether different portions of the T4/Leu3 molecule play important roles for different functions. In addition to test the T4/Leu3-class II MHC antigen interactions, the effects of mAb against class II MHC antigens will be assessed and correlated with T4/Leu3 phenotype. 3) Correlation of T4Leu3 phenotype with susceptibility to systemic lupus erythematosus (SLE). Initial studies have suggested an association between T4 epitope deficiency and development of SLE. Normal individuals, SLE patients, and patients with non-rheumatologic disease will be screened for T4/Leu3 phenotype to confirm these initial observations and to correlate T4/Leu3 phenotype with clinical and serologic manifestations.