PROCESSING OF VIRAL PROTEINS FOR T CELL RECOGNITION

主要组织相容性复合体（MHC）的I类分子包括： 与b2微球蛋白复合的高度多态性重链 （beta2m）。 I类分子由许多蛋白质组成型表达， 体内的细胞类型。 非表达细胞类型的表达发生 在暴露于g-IFN后的免疫应答过程中迅速 和其他细胞因子。 I类分子的唯一功能是 抗原并将其呈递给携带CD 8分子的T细胞（TCD 8+）。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学，参与器官 排斥反应和自身免疫性疾病。 在以下方面取得了迅速进展： 了解抗原I类复合物的物理性质， 抗原是如何产生并与I类分子结合的 在细胞中。 从胞质池产生的8至15个残基的肽 蛋白质被胞质蛋白酶转移到内质网 通过称为TAP的MHC编码的转运蛋白复合物在内质网（ER）中转运。 一旦 在内质网中，肽（可能在进一步被肽酶修整后） 与TAP相关的I类分子结合并被转运到细胞 面 在过去的一年里，我们继续研究大会和 MHC-I类分子的运输，并在许多方面取得了进展。 1）我们开发了抗原的荧光衍生物， 肽，并使用这些探针，使一些新的发现， I类分子和抗原肽的细胞内运输， 2)我们已经研究了抗原肽是如何从蛋白质中产生的 通过将N-连接的糖基化位点插入靶向ER的 分泌蛋白这揭示了一种新的细胞内途径， 蛋白质从ER返回到胞质溶胶。

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.