PROCESSING OF VIRAL PROTEINS FOR T CELL RECOGNITION

主要组织相容性复合体(MHC)的I类分子 一种与b2-微球蛋白复合的高度多态的重链 (Beta2M)。I类分子由许多分子构成地表达 体内的细胞类型。出现非表达细胞类型的表达 在暴露于g-干扰素后的免疫反应过程中迅速 和其他细胞因子。I类分子的唯一功能是结合 并将它们呈递给含有CD8分子的T细胞(TCD8+)。TCD8+ 在根除细胞内病原体和肿瘤方面发挥关键作用。 它们还可以促进免疫病理，参与器官 排斥反应和自身免疫性疾病。在……方面取得了迅速的进展 了解I类抗原复合体的物理性质，并在 抗原是如何产生并与I类分子相联系的 在牢房里。由胞浆池产生的8至15个残基的多肽 通过胞浆蛋白水解酶转位到内质 由MHC编码的转运蛋白复合体TAP表达。一次 在内质网中，多肽(可能在被多肽酶进一步修剪后)结合 与TAP相关的I类分子，并被输送到细胞 浮出水面。在过去的一年里，我们继续研究大会和 MHC I类分子的贩运，并在一些 前沿：1)我们开发了一种抗原性的荧光衍生品 并使用这些探针得出了一些关于 I类分子和抗原肽的细胞内运输， 2)我们研究了抗原肽是如何从蛋白质中产生的 通过在内质网中插入N-连接的糖基化位点来靶向内质网 分泌的蛋白质。这揭示了一种新的细胞内途径，通过这种途径 蛋白质从内质网返回到胞浆。

Class I molecules of the major histocompatibility complex (MHC) consist of a highly polymorphic heavy chain complexed to b2-microglobulin (beta2m). Class I molecules are constitutively expressed by numerous cell types in the body. Expression by non-expressing cell types occurs rapidly in the course of a immune response following exposure to g-IFN and other cytokines. The sole function of class I molecules is to bind antigens and present them to T cell bearing CD8 molecules (TCD8+). TCD8+ play a critical role in eradicating intracellular pathogens and tumors. They can also contribute to immunopathology, being involved in organ rejection and autoimmune diseases. There has been rapid progress in understanding the physical nature of the antigen-class I complex, and in how antigens are generated and become associated with class I molecules in cells. Peptides of 8 to 15 residues produced from a cytosolic pool of proteins by cytosolic proteases are translocated into the endoplasmic reticulum (ER) by a MHC encoded transporter complex known as TAP. Once in the ER, peptides (possibly after further trimming by peptidases) bind to class I molecules associated with TAP and are transported to the cell surface. In the past year we have continued our studies the assembly and trafficking of MHC class I molecules and have made progress on a number of fronts: 1) We developed fluorescent derivatives of an antigenic peptides and used these probes to make several novel findings about the intracellular trafficking of class I molecules and antigenic peptides, 2) We have studied how antigenic peptides are generated from proteins targeted to the ER by inserting a N-linked glycosylation site in a secreted protein. This revealed a novel intracellular pathway by which proteins are returned from the ER to the cytosol.