FUNCTIONAL ANALYSIS OF HUMAN IA

拟议研究的目标是分析人类白细胞抗原II类的作用 人类免疫反应发展的多样性。的表位 破伤风毒素(TTOX)抗原，在以下情况下具有免疫优势 不同的II类分子将被确定。以下问题 将利用L细胞和B细胞转染体进行高表达 单个人类白细胞抗原II类分子水平： 1)不同DR个体的免疫优势表位是否不同 和DQ类型？ 2)DQ限制性反应的相对贡献是多少？ 总反应是什么？ 3)在异性恋个体中，“杂交”DQ的贡献是什么？ 分子对总DQ的响应？是不同的表位 免疫显性？ 4)DQomicron链在DQ限制性反应中的作用是什么？ 5)是否有证据表明ttox反应仅限于混合同型？ 这些分子使用哪些表位？ 6)在以下情况下，DR限制反应是否存在差异 不同的DR4亚型与Will抗原特异性和DR4限制性T细胞 细胞能在多大程度上区分各种DR4亚型？ 7)DR分子的第三高变区(HV)起什么作用 在确定哪些表位是DR限制性的免疫优势时 回应是什么？ 将通过测量a)大量增殖物来分析T细胞反应 反应和b)针对的前体T细胞的频率 不同II类呈递的TTOX抗原多肽片段 转染者。此外，第二类限制性TTOX特异性T细胞 将生成克隆，以研究结构的影响 T细胞识别中II类分子的变异。

The goals of the proposed studies are to analyze the role of HLA class II diversity in the development of immune responses in man. The epitopes of the tetanus toxin (ttox) antigen which are immunodominant in the context of different class II molecules will be determined. The following questions will be addressed using L cell and B cell transfectants expressing high levels of individual HLA class II molecules: 1)Do the immunodominant epitopes differ in individuals of different DR and DQ type? 2)What is the relative contribution of DQ restricted responses to the total response? 3)In heterogygous individuals, what is the contribution of "hybrid" DQ molecules to the total DQ response? Are different epitopes immunodominant? 4)What is the role of the DQomicron( chain in DQ-restricted responses? 5)Is there any evidence of ttox responses restricted to mixed isotypes and which epitopes are used by such molecules? 6)Are there differences in the DR-restricted response in the context of different DR4 subtypes and will antigen-specific and DR4-restricted T cell be able to distinguish the various DR4 subtypes and to what extent? 7)What is the role of the third hypervariable (HV) region of DR molecules in determining which epitopes are immunodominant in DR restricted responses? T cell responses will be analyzed by measuring both a) bulk proliferative responses and b) the frequency of precursor T cells directed against peptide fragments of the ttox antigen presented by different class II transfectants. In addition, class II-restricted ttox-specific T cell clones will be generated in order to study the effects of structural variation in class II molecules on T cell recognition.