BIOLOGY OF AN MHC CLASS I ASSOCIATED MOLECULE

一种独特的免疫隔膜存在于基底板上方 肠道，实际上只有两种细胞类型：肠道 上皮细胞(IEC)和上皮内淋巴细胞(IIEL)。这个 然而，IELS的功能及其与IECS的关系在很大程度上 未知。当然，iIEL定位于基底侧向 表面的IEC，实际上排除了其他单元类型， 其T细胞受体(TCR)的寡克隆性及其优势表达 CD8提示在免疫监视和/或免疫调节中发挥作用。这个 IELs上CD8的优势强烈表明 作为反配体的组织相容性复合体(MHC)I型分子 关于IIEL-IEC相互作用的IEC。进一步定义IEC-EL 相互作用，我们已经确定了一种分子，它表达在 几种单抗对IECs细胞表面的识别作用 根据几个标准，这似乎与{gp180}，MHC有关 Ia类分子，可能还有Ib类分子。这种分子，“34B1” 抗原“因此被放置在一个潜在的关键功能位置上 细胞表面。34B1抗原的初步鉴定显示 以下是鲜明的特点：(L)34B1相对局限于 肠、胆管、肾上皮细胞表达 皮肤、胸腺、粒细胞和活化的T、B细胞；(2)34B1是一种66- 70kD糖蛋白，链内二硫键数目较多； (3)34B1参与细胞-细胞中定义的iIEL-IEC相互作用 以及(4)34B1与MHC I类分子和 (Gpl80)。这些初步数据有力地表明了一个新颖而重要的 这种分子在肠道上皮腔内发挥作用。我们的 具体目标是：(1)克隆、测序和鉴定人和 小鼠34B1基因与基因的关系；(2)研究34B1与 MHC-I类抗原的亚基关联性 转染型突变细胞系和COS细胞；(3)评价 34B1抗原结扎对IECs和IELs的功能影响 确定34B1是否在MHC I类信号转导中起作用； (4)确定34B1抗原的配基。

A unique immunological compartment exists above the basal lamina of the intestine which consists of virtually only two cell types: the intestinal epithelial cell (IEC) and the intraepithelial lymphocyte (iIEL). the function of iIELs and their relationship with IECs is, however, largely unknown. Certainly the localization of the iIEL to the basolateral surface of the IEC to the virtual exclusion of other cell types, the oligoclonality of their T cell receptor (TCR) and dominant expression of CD8 suggests a role in immunosurveillance and/or immunoregulation. The preponderance of CD8 on iIELs strongly implicates major histocompatibility complex (MHC) class I-type molecules as counterligands on the IEC for iIEL-IEC interactions. To further define IEC-EL interactions, we have identified a molecule which is expressed on the cell surface of IECs as defined by several monoclonal antibodies (mAb) that, by several criteria, appears to be associated with {gp180}, MHC class Ia and, possibly, class Ib molecules. This molecule, the "34B1 antigen" is thus placed at a potentially critical functional location on the cell surface. Preliminary characterization of the 34B1 antigen shows the following distinctive features: (l) 34B1 is relatively restricted to expression by epithelial cells of the intestine, biliary tract, kidney, skin, thymus, granulocytes and activated T and B cells; (2) 34B1 is a 66- 70 kD glycoprotein with a high number of intrachain disulfide linkages; (3) 34B1 is involved in iIEL-IEC interactions as defined in a cell-cell adhesion assay; and (4) 34B1 coassociates with MHC class I molecules and (gpl80). These preliminary data strongly suggest a novel and important function for this molecule in the intestinal epithelial compartment. Our specific aims are: (1) to clone, sequence and identify the human and mouse 34B1 cDNA and gene; (2) to investigate the association of the 34B1 antigen with MHC class I by characterizing subunit associations in transfected mutant cell lines and COS cells; (3) to evaluate the functional consequences of 34B1 antigen ligation on IECs and iIELs and determine whether 34B1 functions in transduction of MHC class I signals; and (4) to determine the ligand for the 34B1 antigen.