STUDIES OF HLA CLASS II GENES

建议进行研究以获得有关该基因序列的进一步信息 人类白细胞抗原II类DR和DQ基因的表达 外周血淋巴细胞识别表位在异基因移植物中的表达 受限的识别。纯合分型细胞(HTCs)，来自 任何可能的血缘交配，都将被研究。DR4+和DR2+ HTCS将是拟议的几个实验的主要焦点 原因，包括其中每一个的几个“DW子类型” 已经定义了血清学定义的特异性。个人谁是 根据DW特性，DR4+可分为多个组 它们按照HTC的定义来表达，即T认可的特性 这些“亚型”特异性包括Dw4、Dw10、Dw13、Dw14、 和Dw15。同样，DR2+个体也可以分为表达 DW2、DW12和LD-MN2.我们认为这是一种特殊的力量 DNA技术在同一HTCs研究中的应用 已经并将继续在我们的实验室进行研究，包括 DR和DQ蛋白的研究、功能鉴定 反应性T淋巴细胞，以及识别的决定因素在 你好--而且认可度有限。这应该允许关联 结构，该结构由本申请中的协议确定 功能，从而使我们能够更好地理解 细胞间的相互作用。包括体内在内的许多技术 重组、外显子内改组和定点突变是 建议精确定位哪些序列参与了表达 T淋巴细胞识别的决定因素。正常和突变基因 将通过转染法进行研究。此外，包括 感兴趣的序列将在抗原呈递细胞中进行评估 系统。将尝试产生单抗/抗血清 与利益相关的决定因素。我们相信这些研究将有助于 通过提供研究这一问题所需的背景信息进行诊断 疾病单倍型中的基因家族。

Studies are proposed to obtain further information about sequences of expressed HLA class II DR and DQ genes that are responsible for the expression of determinant recognized by T lymphocytes in allo- or restricted recognition. Homozygous typing cells (HTCs), from consanguineous matings wherever possible, will be studied. DR4+ and DR2+ HTCs will be the primary focus of the proposed experiments for several reasons, including the fact that several "Dw subtypes" of each of these serologically defined specificities have been defined. Individuals who are DR4+ can be divided into a number of groups based on the Dw specificities that they express as defined with HTCs, i.e. specificities recognized by T lymphocytes; these "subtype" specificities include Dw4, Dw10, Dw13, Dw14, and Dw15. Likewise, DR2+ individuals can be divided into those expressing Dw2, Dw12, and LD-MN2. We consider it a special strength of this application that the same HTCs proposed herein for study by DNA techniques have been, and are continuing to be, studied in our laboratories including studies of the DR and DQ proteins, functional characterization of responding T lymphocytes, and definition of determinants recognized in allo- and restricted recognition. This should allow correlations of structure as determined by protocols in the present application with function and thus allow a better understanding of the molecular basis of cellular interactions. A number of techniques, including in vivo recombination, intra-exonic shuffling and site directed mutagenesis, are proposed to pinpoint precisely which sequences are involved in expression of determinants recognized by T lymphocytes. Normal and mutagenized genes will be studied by transfection. In addition, peptides which include sequences of interest will be evaluated in an antigen presenting cell system. Attempts will be made to generate monoclonal antibodies/antisera to determinants of interest. We believe these studies will contribute to diagnosis by providing the background information needed to study this same gene family in "disease haplotypes".