CELL BIOLOGY OF BCR MEDIATED ANTIGEN PROCESSING

描述(改编自申请人的摘要)：中心假设 在这个项目中要追求的是特定抗原的呈递 B细胞发生在一个特殊的亚细胞室(S)。初步 研究已经确定了两个候选隔室，称为II类囊泡 (CIIV)和多层II类小泡(MCV)。CIIV包含两者 内化的B细胞抗原受体(BCR)和II类分子， 提示一部分内化的抗原-bcr复合体可能是 从大量的内吞途径转移到CIIV，在那里处理和 多肽片段被装载到第二类分子上。MCV是一种 不同的细胞内隔间，也包含II类分子，如 以及一个未知的46 kDa标记蛋白。该项目将使用 生物化学纯化的CIIV和MCV制剂阐明其作用 在处理bcr相关抗原的过程中，这些特殊的隔室。 此外，还将使用各种bcr突变体来鉴定该序列 负责将携带抗原的bcr分选为CIIV的决定因素 和MCV。

DESCRIPTION (Adapted from the Applicant's Abstract): The central hypothesis to be pursued in this project is that the presentation of specific antigens by B cells occurs in a specialized subcellular compartment(s). Preliminary studies have identified two candidate compartments termed Class II vesicles (CIIV) and multilaminar Class II vesicles (MCV). CIIV contain both internalized B-cell antigen receptors (BCR) and Class II molecules, suggesting that a fraction of internalized antigen-BCR complexes may be diverted from the bulk endocytic pathway into CIIV, where processing and loading of peptide fragments onto Class II molecules occurs. MCV are a distinct intracellular compartment that also contains Class II molecules, as well as an unidentified 46 kDa marker protein. This project will use biochemically purified preparations of CIIV and MCV to clarify the roles of these specialized compartments in the processing of BCR-associated antigens. In addition, various BCR mutants will be used to identify the sequence determinants responsible for the sorting of antigen-bearing BCR into CIIV and MCV.