Using the model system of the murine immune response to the vesicular stomatitis virus (VSV) G protein, studies on the regulation and specificity of the immune response to viruses will be performed. These studies will provide critical insights into cellular immunology. Fine structural analysis of the thymus derived (T cell ) lymphocyte clones and hybridomas elicited in immunized mice and the epitopes they recognize will be undertaken. Both CD4+ and CD8+ G-reactive T cells will be studied; the MHC restriction of the epitopes recognition will be defined. The sequences recognized by the T cells will be characterized by a variety of methods including: infections vs. killed virus wild type vs. defective interfering virus, purified G protein micelles or isolated trimers of truncated soluble Gs, serotype (NJ vs Indiana) restriction, field isolates, vaccinia-G vectors, transfected antigen presenting cells (APCs), proteolytic peptides of G, lacZ fusion proteins, synthetic oligopeptides. Cytokines secreted upon stimulation will be characterized by bioassay, ELISA, or in situ hybridization. The clones/hybridomas will be characterized for utilization of T cell receptor (TCR) variable region genes, and anti-idiotypic (anti-ID) reagents will be generated and used in studies of immunization and perturbation of the hybridomas will be studied both in vitro and in vivo. The influence of the hosts genotype on the epitopes recognized and the IDs utilized will be examined. Whether T cell or B cell immunity, or a combination of both is critical for immune protection will be studied. The influence of loss of principal restricting elements on the hosts' response will be investigated. The techniques used in the pursuit range from basic cellular immunologic culture and assays of T cells, to molecular cloning and transfections, in situ hybridization, biochemical isolation of fragments and fusion proteins, cell biology viral infection of living hosts, and viral propagation in vitro.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018083-14
Application #
2060630
Study Section
Virology Study Section (VR)
Project Start
1981-08-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
14
Fiscal Year
1994
Total Cost
Indirect Cost
Name
New York University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Plakhov, I V; Aoki, C; Reiss, C S et al. (1995) Pathogenesis of murine encephalitis limited by defective interfering particles. An immunohistochemical study. J Neurovirol 1:207-18
Huneycutt, B S; Bi, Z; Aoki, C J et al. (1993) Central neuropathogenesis of vesicular stomatitis virus infection of immunodeficient mice. J Virol 67:6698-706
Reiss, C S; Gapud, C P; Keil, W (1992) Newly synthesized class II MHC chains are required for VSV G presentation to CTL clones. Cell Immunol 139:229-38
Browning, M J; Huneycutt, B S; Huang, A S et al. (1991) Replication-defective viruses modulate immune responses. J Immunol 147:2685-91
Forger 3rd, J M; Bronson, R T; Huang, A S et al. (1991) Murine infection by vesicular stomatitis virus: initial characterization of the H-2d system. J Virol 65:4950-8
Pena-Cruz, V; Reiss, C; McIntosh, K (1991) Effect of respiratory syncytial virus infection on mice with protein malnutrition. J Med Virol 33:219-23
Browning, M J; Huang, A S; Reiss, C S (1990) Cytolytic T lymphocytes from the BALB/c-H-2dm2 mouse recognize the vesicular stomatitis virus glycoprotein and are restricted by class II MHC antigens. J Immunol 145:985-94
Browning, M; Reiss, C S; Huang, A S (1990) The soluble viral glycoprotein of vesicular stomatitis virus efficiently sensitizes target cells for lysis by CD4+ T lymphocytes. J Virol 64:3810-6
Pena-Cruz, V; Reiss, C S; McIntosh, K (1989) Sendai virus infection of mice with protein malnutrition. J Virol 63:3541-4