BIOLOGY OF AN MHC CLASS I ASSOCIATED MOLECULE

一个独特的免疫区室存在于基底层之上， 肠实际上只由两种类型的细胞组成： 上皮细胞（IEC）和上皮内淋巴细胞（iIEL）。的 然而，iIEL的功能及其与IEC的关系在很大程度上 未知当然，iIEL在基底外侧的定位 IEC的表面，以虚拟排除其他细胞类型， T细胞受体（TCR）的寡克隆性和 CD 8提示在免疫监视和/或免疫调节中的作用。的 CD 8在iIEL上的优势强烈暗示了主要的 作为反配体的组织相容性复合体（MHC）I类分子 在IEC上进行iIEL-IEC交互。进一步定义IEC-EL 相互作用，我们已经确定了一种分子， IEC的细胞表面，由几种单克隆抗体（mAb）定义 根据几个标准，似乎与{gp 180}，MHC Ia类和可能的Ib类分子。这个分子，34 B1 因此，“抗原”被置于 细胞表面。34 B1抗原的初步表征显示， （1）34 B1相对局限于 通过肠、胆道、肾 皮肤、胸腺、粒细胞和活化的T和B细胞;（2）34 B1是66- 70 kD糖蛋白，具有大量的链内二硫键; (3)34 B1参与如在细胞-细胞通信中定义的iIEL-IEC相互作用。 粘附测定;和（4）34 B1与MHC I类分子共缔合， （gpl80）。这些初步数据强烈表明， 这种分子在肠上皮隔室中的功能。我们 具体目标是：（1）克隆、测序和鉴定人， 小鼠34 B1基因的cDNA和基因序列;（2）研究34 B1基因与小鼠34 B1基因的关系， 抗原与MHC I类通过表征亚基协会， 转染的突变体细胞系和COS细胞;（3）评估 34 B1抗原连接对IEC和iIEL的功能影响， 确定34 B1是否在MHC I类信号转导中起作用; 和（4）确定34 B1抗原的配体。

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.