CLASS II GENES IN AUTOIMMUNE ANIMALS

II类分子在正常和异常中都起着核心作用 免疫反应和一些自身免疫性疾病 老鼠似乎与第二类分子相连。我们建议评估 II类分子的定性和定量贡献 从NZW小鼠品系到(NZWxNZB)F小鼠的自身免疫。这个 分子中II类分子的定性结构功能关系 自身免疫性将通过寻找NZW基因中的不寻常序列来评估。 我们将开发针对NZW/NZB的单抗 杂化II类分子来检查杂化II类分子 ，并确定这些杂化分子是否可能对 自身免疫的发展。使用转基因技术，我们还将 确定“u”单倍型是否是免疫显性的，这将有助于 解释NZW对加速自身免疫的贡献。此外，我们 计划生产转基因NZB小鼠，其中NZW II类转基因 放入NZB小鼠体内。 评估是否存在II类的数量贡献 我们将分离NZB和NZW基因并检测 调节类基因表达的顺式和反式作用因子 II基因。顺位作用因素将通过确定是否 NZW和NZB的II类基因5‘侧翼区有异常 序列。编码反式作用因子的基因将被分离出来 西南方法学，由此标记的寡核苷酸对应于 NZB和NZW 5‘调控区用于探测NZB和NZW lambda Gt11文库。这些cdna将被检查以寻找不寻常的序列。 这些研究将对定量和定性两方面进行评估 第二类基因对自身免疫的贡献。

The class II molecules play a central role in both normal and abnormal immune responses, and a number of autoimmune diseases both in man and mouse appear to be linked to class II molecules. We propose to evaluate the qualitative and quantitative contribution of the class II molecules from the NZW mouse strain to autoimmunity in the (NZWxNZB)F mouse. The qualitative structure function relationship of class II molecules in autoimmunity will be evaluated by seeking unusual sequences in NZW cDNA's. We will develop monoclonal antibodies specific for the NZW/NZB hybrid class II molecules to examine whether hybrid class II molecules exist in vivo, and determine if these hybrid molecules might contribute to the development of autoimmunity. Using transfections we will also determine whether the "u" haplotype is immunodominant, which would help explain the NZW contribution to accelerated autoimmunity. In addition, we plan to produce transgenic NZB mice, in which NZW class II transgenes are placed into NZB mice. To evaluate whether there is a quantitative contribution of class II molecules to autoimmunity, we will isolate NZB and NZW genes and examine both cis and trans acting factors which regulate the expression of class II genes. Cis acting factors will be evaluated by determining whether the 5' flanking region of the class II genes of NZW and NZB have unusual sequences. cDNA's encoding trans acting factors will be isolated by a Southwestern methodology whereby labeled oligonucleotides corresponding to the NZB and NZW 5' regulatory regions are used to probe NZB and NZW lambda gt11 libraries. These cDNA's will be examined for unusual sequences. These studies will evaluate both the quantitative and qualitative contributions of class II genes to autoimmunity.