INVARIANT CHAIN AND ANTIGEN PRESENTATION

主要组织相容性复合体（MHC）分子负责 将抗原呈递给T细胞 两个结构相似的 I类和II类分子已经进化出结合槽 可以容纳多种肽抗原。 当一个特定的MHC 分子可能只能结合宇宙的一小部分， 抗原肽，存在多种同种和等位形式的抗原肽， I类和II类分子确定了物种有能力 呈现大多数抗原。 然而相似的I类和II类分子 关于肽结合，它们呈现不同的肽 起源于vivo。 因此，I类分子主要与 来源于通过I类表达的多肽制备的蛋白质的肽 细胞，而II类分子通常从 外源性蛋白质，它们通过免疫系统被导入细胞， 内吞作用 造成这种二分法的机制很差， 可以理解，但一个贡献因素是不变链（Ii）。 这 一种与内质网中II类链相关的分子 (ER)并阻止肽与II类分子结合。 运输后 到后高尔基体隔室，Ii被释放，II类分子 能够获得肽。 因此，Ii可能是最重要的一个 负责外源肽的II类结合的因子。 为了完成它的任务，Ii被赋予了结构基序， 将各种形式的分子靶向不同的亚细胞， 隔间 这些目标信号的确切性质将是 测定 亚细胞分级分析和形态学 分析将揭示Ii的各种形式在 细胞到达目的地。 这些分析将揭示类 II分子获得肽。 这些信息将是非常宝贵的， 设计新的疫苗，并应阐明自我分子如何 可能会引起自身免疫反应

The major histocompatibility complex (MHC) molecules are responsible for the presentation of antigens to T cells. Two structurally similar types of molecules, class I and class II, have evolved binding grooves that can accommodate a variety of peptidic antigens. While a given MHC molecule may only be able to bind a subfraction of the universe of antigenic peptides, the existence of multiple iso- and allelic forms of the class I and II molecules ascertain that the species has the capacity of present most antigens. However similar class I and class II molecules are with regard to peptide binding, they present peptides of different origins in vivo. Thus, class I molecules primarily associate with peptides derived from proteins manufactured by the class I-expressing cell while the class II molecules usually obtain their peptides from exogenous proteins, which have been imported into the cell by endocytosis. The mechanisms responsible for this dichotomy are poorly understood but one contributing factor is the invariant chain (Ii). This molecule associates with class II chains in the endoplasmic reticulum (ER) and prevents peptide binding to class II molecules. After transport to a post-Golgi compartment, Ii is released and the class II molecules are able to acquire peptides. Thus, Ii may be the most important single factor responsible for the class II binding of exogenous peptides. To accomplish its task, Ii is endowed with structural motifs that targets various forms of the molecules to different subcellular compartments. The precise nature of these targeting signals will be determined. Subcellular fractionation analyses and morphological analyses will reveal which routes the various forms of Ii take in the cell to reach their destinations. These analyses will reveal where class II molecules obtain peptides. Such information will be invaluable in designing novel vaccines and should shed light on how self-molecules might give rise to auto-immune reactions.