STRUCTURE AND FUNCTION OF PEPTIDE TRANSPORTERS

CD 8 + T细胞（T/CD 8+）在控制病毒感染中发挥重要作用 感染. T/CD 8+识别来自以下的8至10个残基的肽： 位于病毒感染细胞的胞质溶胶中的病毒蛋白。 这些 肽在与I类分子的复合物中被识别， 主要组织相容性复合体（MHC） 在过去的三年里， 发现MHC还编码两种分子，称为TAP 1和TAP 2， 它们以1：1的比例联合收割机结合形成一种复合物， 将肽从胞质溶胶转运到内质网（ER）中。 人类TAP基因显示至少一些有限的多态性。 的 这些肽泵的存在及其多态性引起了一些 重要的问题：细胞中的泵位于何处？ 做 泵影响由I类分子呈递的肽的类型？ 泵是否与产生抗原肽的蛋白酶相连 在细胞质中 泵是如何工作的？ 有没有人 TAP基因突变导致的免疫缺陷 Can细胞 通过其他机制运输肽？ 为了帮助描述 TAP基因的结构和功能，我们已经创建重组 表达TAP 1（VV-TAP 1/h）、TAP 2（VV-TAP 1/h）或TAP 3（VV-TAP 1/h）的牛痘病毒（rVV）， TAP 2/h）或TAP 1和TAP 2（VV-TAP [1&2]/h）。 我们已经证明 每个rVV表达功能亚基，或者在VV-1的情况下， TAP[1&2]/h，一种功能性转运蛋白。 使用这个rVV面板，我们有 研究了组装、细胞内定位和生化特性 TAP 1和TAP 2，并与其他实验室合作， 证明疱疹病毒蛋白结合人TAP并阻断其表达。 功能

CD8+ T cells (T/CD8+) play an important role in controlling virus infections. T/CD8+ recognize peptides of 8 to 10 residues derived from viral proteins located in the cytosol of virus infected cells. These peptides are recognized in a complex with class I molecules encoded by the major histocompatibility complex (MHC). In the past 3 years it was discovered that the MHC also encodes two molecules, termed TAP1 and TAP2, that combine in a 1:1 ratio to create a complex that specifically transports peptides from the cytosol into the endoplasmic reticulum (ER). Human TAP genes display at least some limited polymorphism. The existence of these peptide pumps and their polymorphism raises a number of important questions: Where in the cells are the pumps located? Do the pumps influence the types of peptides presented by class I molecules? Are the pumps tethered to the proteases that produce antigenic peptides in the cytosol? How do the pumps work? Are there individuals with immune deficiencies based on mutations in the TAP genes? Can cells transport peptides via other mechanisms? To help characterize the structure and function of the TAP genes we have created recombinant vaccinia viruses (rVV) that express either TAP1 (VV-TAP1/h), TAP2 (VV- TAP2/h), or TAP1 and TAP2 (VV-TAP[1&2]/h). We have demonstrated that each of rVVs express functional subunits, or in the case of the VV- TAP[1&2]/h, a functional transporter. Using this panel of rVVs we have studied the assembly, intracellular location, and biochemical properties of TAP1 and TAP2, and in collaboration with other laboratories, demonstrated that a herpesvirus protein binds human TAP and blocks its function.