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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI040236-04
Application #
2887275
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Ridge, John P
Project Start
1996-06-01
Project End
2001-05-31
Budget Start
1999-06-01
Budget End
2000-05-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Trudeau Institute, Inc.
Department
Type
DUNS #
City
Saranac Lake
State
NY
Country
United States
Zip Code
12983
Putnam, Michelle A; Moquin, Amy E; Merrihew, Megan et al. (2003) Lipid raft-independent B cell receptor-mediated antigen internalization and intracellular trafficking. J Immunol 170:905-12
Gondre-Lewis, T A; Moquin, A E; Drake, J R (2001) Prolonged antigen persistence within nonterminal late endocytic compartments of antigen-specific B lymphocytes. J Immunol 166:6657-64