The B cell antigen receptor (BCR) enhances the presentation of antigen to T cells over 1000-fold by, in part, delivering antigen to specific compartment(s) within the cell where it is processed for loading onto MHC class II. A newly identified intracellular structure, antigen receptor induced subcellular complex (ARISC), is seen in a mouse B cell line following antigen receptor (BCR) engagement. The principal investigator and his colleagues propose that: 1) The ARISC is necessary for the BCR facilitated presentation of some antigens and 2) The ARISC is a consequence of one or more signals that emanate from the BCR and that these same pathways are utilized by the Nef protein. These hypotheses will be tested in the aims 1) Characterize the ARISC and establish its significance in vivo, and 2) Elucidate the signaling mechanisms involved in ARISC formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056187-03
Application #
6019309
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Serrate-Sztein, Susana
Project Start
1997-09-30
Project End
2001-09-29
Budget Start
1999-09-30
Budget End
2001-09-29
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Siemasko, Karyn; Skaggs, Brian J; Kabak, Shara et al. (2002) Receptor-facilitated antigen presentation requires the recruitment of B cell linker protein to Igalpha. J Immunol 168:2127-38
Kabak, Shara; Skaggs, Brian J; Gold, Michael R et al. (2002) The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways. Mol Cell Biol 22:2524-35
Siemasko, K; Clark, M R (2001) The control and facilitation of MHC class II antigen processing by the BCR. Curr Opin Immunol 13:32-6
Siemasko, K; Eisfelder, B J; Stebbins, C et al. (1999) Ig alpha and Ig beta are required for efficient trafficking to late endosomes and to enhance antigen presentation. J Immunol 162:6518-25
Siemasko, K; Eisfelder, B J; Williamson, E et al. (1998) Cutting edge: signals from the B lymphocyte antigen receptor regulate MHC class II containing late endosomes. J Immunol 160:5203-8