The processing and presentation of antigen by B cells to helper T cells is a central event in the initiation of T-cell dependent antibody responses. Processing involves the conversion of protein antigens that are displayed bound to the Major Histocompatibility Complex class II molecules (MHC class II) on the surfaces of B cells for the recognition by T cells. Specific B cells bind native antigen to the B cell antigen receptor (BCR) on the cell surface and the bound antigen is subsequently internalized and delivered to an appropriate subcellular compartment for processing. BCR-mediated antigen processing is highly efficient. The BCR plays at least two crucial roles in antigen processing which are: (1) to capture antigens on the cell surface and deliver them to the subcellular compartments for processing, and (2) upon cross-linking by antigen, to initiate a signal transduction cascade that regulates antigen processing. At present, the molecular basis of both functions of the BCR is not understood. The BCR is a multi-component complex consisting of an antigen binding component, the membrane immunoglobulin (mIg), and a signal transducing component, the disulfide-linked Iga/Igb heterodimer. The goal of this proposal is to define the function of BCR in antigen processing at a molecular level.
The aims of this proposal are 1) to characterize the BCR-mediated antigen transport pathway, 2) to identify the discrete steps in the BCR trafficking that are regulated by BCR-mediated signal transduction, 3) to determine which components of BCR are necessary for the BCR-mediated antigen processing and 4) to identify the structural elements carried by BCR complex that are required for antigen transport and for the regulation of this transport. The results of these studies will help us to gain the ability to control antigen processing and provide the strategies for the design of effective vaccines and therapies for autoimmune diseases.
| Brown, B K; Li, C; Cheng, P C et al. (1999) Trafficking of the Igalpha/Igbeta heterodimer with membrane Ig and bound antigen to the major histocompatibility complex class II peptide-loading compartment. J Biol Chem 274:11439-46 |
