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IMMUNOGENICITY OF LISTERIA-DERIVED ANTIGENS

Award Number: R01AI064576
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2005
PERIOD OF PERFORMANCE END DATE: 01/31/2010

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IMMUNOGENICITY OF LISTERIA-DERIVED ANTIGENS - DESCRIPTION (provided by applicant): Priming of pathogen-specific CDS T cell responses involves the recognition of pathogen-derived, antigenic peptides in the context of MHC class I molecules on the surface of professional antigen presenting cells (pAPC). These peptides are generated upon intracellular degradation of pathogen-derived proteins by a cellular protease complex, the proteasome. pAPC and cells exposed to inflammatory cytokines express a number of inducible proteasome components which modify the catalytic activity of proteasomes and accelerate the generation of many antigenic peptides. CDS T cell responses to infections are often focused towards single "immunodominant" epitopes. Many immunodominant antigenic peptides: 1), derive from antigens that are rapidly degraded within host cells; and 2), are rapidly generated by the modified form of the proteasome. Based on these observations, we propose that these antigenic peptides that appear the earliest on the cell surface of pAPC following infection will be the most potent in inducing CDS T-cell responses. In aim 1 we will test this hypothesis by infecting normal and genetically modified mice that lack the inducible proteasome components with recombinant Listeria monocytogenes. CDS T-cell responses to rapidly and slowly degraded Listeria antigens and to rapidly and slowly generated Listeria peptides will be examined. Our studies will show whether the relative rates with which antigenic peptides are generated determine their capacity to prime CDS T cell responses. In aim 2, we will determine in which cells immunodominance is decided. Mice that express the inducible proteasome components in specific cell types only will be generated and tested for their ability to mount responses to peptides that are inefficiently generated by the unmodified type of proteasome. These experiments will show whether antigen processing events in infected cells or in cross-presenting pAPC are decisive for the priming of CDS T cell responses. These studies will enlarge our understanding of the determinants of immunodominance and are of great importance for vaccine design.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2009 ( Subtotal = $200,916 )
2009	2009	UTRECHT UNIVERSITY MEDICAL SCHOOL	HEIDELBERGLAAN 100 3584 CG	UTRECHT				NLD	Allergy and Infectious Diseases Research	001	6	7/2/2009	NON-COMPETING CONTINUATION	$20,092
2009	2009	UTRECHT UNIVERSITY MEDICAL SCHOOL	HEIDELBERGLAAN 100 3584 CG	UTRECHT				NLD	Allergy and Infectious Diseases Research	000	6	1/28/2009	NON-COMPETING CONTINUATION	$180,824
														Subtotal = $200,916

Issue Date FY: 2007 ( Subtotal = $204,807 )
2007	2007	UTRECHT UNIVERSITY MEDICAL SCHOOL	HEIDELBERGLAAN 100 3584 CG	UTRECHT				NLD	Allergy and Infectious Diseases Research	000	4	2/5/2007	NON-COMPETING CONTINUATION	$204,807
														Subtotal = $204,807

Issue Date FY: 2006 ( Subtotal = $210,924 )
2006	2006	UTRECHT UNIVERSITY MEDICAL SCHOOL	HEIDELBERGLAAN 100 3584 CG	UTRECHT				NLD	Allergy and Infectious Diseases Research	000	3	2/10/2006	NON-COMPETING CONTINUATION	$210,924
														Subtotal = $210,924

Issue Date FY: 2005 ( Subtotal = $312,000 )
2005	2005	UNIVERSITY OF ROCHESTER	1325 MOUNT HOPE AVE, SUITE 260	ROCHESTER	NY	14620	MONROE	USA	Microbiology and Infectious Diseases Research	000	1	1/31/2005	NEW	$312,000
														Subtotal = $312,000

Grand Total All Awards = $928,647

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IMMUNOGENICITY OF LISTERIA-DERIVED ANTIGENS

Award Number: R01AI064576

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2005

PERIOD OF PERFORMANCE END DATE: 01/31/2010

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