Class I MHC (MHC-I) molecules primarily present endogenous antigens, i.e. antigens that are present in the cytosol and are subject to the cytosolic processing mechanisms that comprise the conventional MHC-I processing pathway. However, exogenous antigens can also be presented by MHC-I molecules under certain circumstances, particularly in the case of particulate antigens. Recently, considerable attention has been focused on mechanisms that may contribute to alternate MHC-I processing pathways. Divergent results in several different systems have suggested that more than one alternate processing mechanism may exist. In some cases, MHC-I molecules present vacuolar antigens via alternate MHC-I processing mechanisms that are quite distinct from the conventional MHC- I processing pathway. These mechanisms may play important roles in generating CD8 T cell responses, especially to antigens expressed by vacuolar microorganisms and tumor cells. This project will define the mechanisms involved in the alternate MHC-I processing of several different types of exogenous antigens (intravacuolar bacteria and particulate vaccines). These studies may elucidate the basis of CD8 T cell responses to intravacuolar pathogens, such as Leishmania, Salmonella, and Toxoplasma species, and Mycobacterium tuberculosis. These studies also apply to tumor immunology and the role of alternate MHC-I processing mechanisms in the genesis of anti-tumor CD8 T cell responses. In addition, these studies will provide basic information that may be applied to develop strategies of therapeutic immunization to achieve protective CD8 T cell responses with non-viable vaccine preparations, in the absence of the endogenous antigen synthesis that is provided by live viral vaccine preparations. The use of non-viable particulate vaccines would be a safer way to elicit CD8 immunity in immunocompromised patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034343-06
Application #
2886847
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Ridge, John P
Project Start
1994-09-01
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Pathology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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