This project represents and integrated approach for evaluating several molecular aspects of B lymphocyte function. The unifying theme of the program is the study of the two types of polymorphic molecules that serve as both receptors and recognition sites on the B cell membrane, immunoglobulin (Ig) and major histocompatibility complex-encoded class I and class II molecules. The program is composed of three research projects and a core facility, whose function is to provide various support services. In project I, Dr. Corley will analyze the antigenic and idiotypic diversity of the immunoglobulin repertoire specific for senescent erythrocytes. As a major component of this study, he will determine the number and sequences of the germ line genes encoding this response, and ask if somatic events alter the nature of the response to this endogenous autoantigen. Since the idiotypic profile of this response is controlled by Ir genes, this study should advance our understanding of the interrelationship between recognition of class II molecules and immunoglobulin expression. In project II, Dr. Argon will study the intracellular transport of class II and immunoglobulin molecules in cells of the B lineage, and identify the compartments in which post-translational modifications occur. The transport of these endogenous molecules will be compared with that of an exogenous viral glycoprotein in infected B cells. Dr. Argon is using a drug that reversibly inhibits the intracellular transport of membrane and secretory proteins. This work may provide ways to modulate the surface expression and secretion of various molecules. Dr. Cresswell, in project III, will complement these studies by evaluating the interactions between the intracellular transport pathways of class I and class II molecules, and the endocytic pathways taken by internalized ligands. The role of the class II antigen-associated invariant chain in class II transport will also be examined, using invariant chain-negative mutants of B cell lines. He will also antigens following lysosomal degradation. Results from these three projects will enhance our understanding of how B lymphocytes recognize, respond to, and process antigens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI023282-02
Application #
3091701
Study Section
(SRC)
Project Start
1986-09-30
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Davis, J E; Cresswell, P (1990) Lack of detectable endocytosis of B lymphocyte MHC class II antigens using an antibody-independent technique. J Immunol 144:990-7
Wiest, D L; Burkhardt, J K; Hester, S et al. (1990) Membrane biogenesis during B cell differentiation: most endoplasmic reticulum proteins are expressed coordinately. J Cell Biol 110:1501-11
Roche, P A; Cresswell, P (1990) High-affinity binding of an influenza hemagglutinin-derived peptide to purified HLA-DR. J Immunol 144:1849-56
Cresswell, P; Blum, J S; Davis, J E et al. (1990) Transport and expression of HLA class-II glycoproteins. Immunol Res 9:190-9
Marks, M S; Blum, J S; Cresswell, P (1990) Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens. J Cell Biol 111:839-55
Conger, J D; Sage, H J; Corley, R B (1989) Diversity in the available repertoire of murine antibodies reactive with bromelain-treated isologous erythrocytes. J Immunol 143:4044-52
Cresswell, P; Blum, J S; Marks, M S et al. (1989) Structural and functional aspects of HLA class II glycoproteins and the associated invariant chain. Cold Spring Harb Symp Quant Biol 54 Pt 1:309-18
Burkhardt, J K; Argon, Y (1989) Intracellular transport of the glycoprotein of VSV is inhibited by CCCP at a late stage of post-translational processing. J Cell Sci 92 ( Pt 4):633-42
Burkhardt, J K; Hester, S; Argon, Y (1989) The glycoprotein of VSV accumulates in a distal Golgi compartment in the presence of CCCP. J Cell Sci 92 ( Pt 4):643-54
McKinnon, K P; Dunlevy, J R; Dawson, J R et al. (1988) Cell-mediated cytotoxicity and the reorientation of effector cell granules towards the target cell are inhibited by the protonophore carbonylcyanide m-chlorophenylhydrazone. Hum Immunol 22:81-95

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