Studies continue to focus on the role of cytotoxic T lymphocytes (CTL) in host immunity to viruses, using the murine response to type A influenza viruses as a model system. In previous work we have shown that recombinant vaccinia viruses containing cloned influenza virus genes can be used to both stimulate cytotoxic T lymphocytes (CTL) in vivo and in vitro, and to sensitize target cells for lysis by anti-influenza virus CTL. We found that contrary to expectations, a viral internal protein is recognized by anti-influenza CTL more efficiently than the major viral glycoprotein. Experiments will be continued at both population and clonal levels using vaccinia recombinants containing 7 influenza virus structural genes and 3 non-structural genes to further define the importance of individual virus gene products in the anti-influenza virus CTL response. We also propose to further study the role of CTL in modulating lethal and sublethal influenza pneumonia. The in vivo activities of CTL populations and cloned CTL cell lines will be correlated with their specificity for individual viral components and their production of gamma interferon. These studies will include an investigation of the immune mechanisms underlying our finding that immunization with recombinant vaccinia viruses protects mice against lethal influenza pneumonia. Finally, we propose to study the influence of the major histocompatibility complex in the recognition of individual viral components. This will include determining the class I MHC restruction elements for each of the viral components recognized as well as an examination of the phenomenon of MHC associated CTL low responsiveness to influenza virus.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Virology Study Section (VR)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wistar Institute
United States
Zip Code
Eichelberger, M; McMickle, A; Blackman, M et al. (1995) Functional analysis of the TCR alpha- beta+ cells that accumulate in the pneumonic lung of influenza virus-infected TCR-alpha-/- mice. J Immunol 154:1569-76
Wysocka, M; Eisenlohr, L C; Otvos Jr, L et al. (1994) Identification of overlapping class I and class II H-2d-restricted T cell determinants of influenza virus N1 neuraminidase that require infectious virus for presentation. Virology 201:86-94
Hackett, C J; Horowitz, D; Wysocka, M et al. (1992) Influenza virus infection elicits class II major histocompatibility complex-restricted T cells specific for an epitope identified in the NS1 non-structural protein. J Gen Virol 73 ( Pt 6):1339-43
Hackett, C J; Horowitz, D; Wysocka, M et al. (1991) Immunogenic peptides of influenza virus subtype N1 neuraminidase identify a T-cell determinant used in class II major histocompatibility complex-restricted responses to infectious virus. J Virol 65:672-6
Hackett, C J; Yewdell, J W; Bennink, J R et al. (1991) Class II MHC-restricted T cell determinants processed from either endosomes or the cytosol show similar requirements for host protein transport but different kinetics of presentation. J Immunol 146:2944-51
Wysocka, M; Hackett, C J (1990) Class I H-2d-restricted cytotoxic T lymphocytes recognize the neuraminidase glycoprotein of influenza virus subtype N1. J Virol 64:1028-32
Gupta, R; Yewdell, J W; Olmsted, R A et al. (1990) Primary pulmonary murine cytotoxic T lymphocyte specificity in respiratory syncytial virus pneumonia. Microb Pathog 9:13-8
Wysocka, M; Korngold, R; Yewdell, J et al. (1989) Target and effector cell fusion accounts for B lymphocyte-mediated lysis of mouse hepatitis virus-infected cells. J Gen Virol 70 ( Pt 6):1465-72
Eager, K B; Hackett, C J; Gerhard, W U et al. (1989) Murine cell lines stably expressing the influenza virus hemagglutinin gene introduced by a recombinant retrovirus vector are constitutive targets for MHC class I- and class II-restricted T lymphocytes. J Immunol 143:2328-35
Wysocka, M; Bennink, J R (1988) Limiting dilution analysis of memory cytotoxic T lymphocytes specific for individual influenza virus gene products. Cell Immunol 112:425-9

Showing the most recent 10 out of 21 publications