Wednesday, June 18, 2025 6/18/2025

Defining the Unique Properties of the Distinct Signaling Machinery Used by the TCR

Award Number: P01AI091580
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: 07/15/2011
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Defining the Unique Properties of the Distinct Signaling Machinery Used by the TCR - OVERALL PROJECT SUMMARY/ABSTRACT This application is a revision of a renewal of an ongoing Program Project in which five investigators with different but complementary expertise have worked together for 10 years to understand poorly characterized but fundamentally important aspects of TCR signaling. Synergy resulting from interactions and collaborations has yielded impressive progress. The Program benefitted enormously from the complementary expertise, skills and approaches by the 5 investigators from structural biology, proteomics, immunology, biophysics, imaging and computational biology. In addition to the synergy created by the distinct expertise of each of the investigators and the progress we have made over the previous 10 years, we also take advantage of a Proteomics Core that has extended our strategies and analytic skills in proteomics. Our collaborative studies have resulted in considerable progress and productivity. In this revision, a major change that we have made is an increase in the number of projects from 2 to 4 in order to allow for more fully developed aims and approaches to answer the following unanswered questions: 1) What are the unique features of the kinases employed by TCR that have been optimized for regulating critical downstream tyrosine phosphorylation and for unique characteristics involved in ligand discrimination? 2) What are the properties of the circuitry that allow for discrimination of self-pMHC from agonist-pMHC recognition to establish a stable homeostatic state versus a robust cellular response? 3) How is the adaptor LAT condensation regulated and serve to coordinate and amplify the diverse signaling events associated with a robust cellular response? 4) How does the TCR signaling network regulate Ras guanine nucleotide exchange factors (GEFs) with downstream, canonical and non-canonical effector kinase signals in a properly regulated and faithful manner to incoming TCR signals? To answer these questions, a new Project is now incorporated into this proposal to address each of these issues. Our overall goal then is to capitalize on our current progress and leverage our distinct knowledge and skills related to TCR signaling to more completely understand the distinct features of the molecules, the circuitry and the regulation of TCR signaling that enables and ensures appropriate biological responses.


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: 2025 ( Subtotal = $1,968,804 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	14	4/25/2025	NON-COMPETING CONTINUATION	$1,968,804
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	13	4/21/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,968,804

Issue Date FY: 2024 ( Subtotal = $2,064,573 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	13	4/24/2024	NON-COMPETING CONTINUATION	$1,980,254
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	13	4/25/2024	SUPPLEMENT FOR EXPANSION	$84,319
2024	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	003	11	5/30/2024	COMPETING CONTINUATION	$66,130
2024	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	10	5/30/2024	NON-COMPETING CONTINUATION	-$66,130
														Subtotal = $2,064,573

Issue Date FY: 2023 ( Subtotal = $2,055,922 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	12	4/28/2023	NON-COMPETING CONTINUATION	$1,991,529
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	12	8/14/2023	SUPPLEMENT FOR EXPANSION	$64,393
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	12	9/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,055,922

Issue Date FY: 2022 ( Subtotal = $1,999,873 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	11	4/29/2022	COMPETING CONTINUATION	$1,999,873
2022	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	10	4/29/2022	NON-COMPETING CONTINUATION	$0
2022	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	10	2/10/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,999,873

Issue Date FY: 2020 ( Subtotal = $2,466,048 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	10	7/2/2020	NON-COMPETING CONTINUATION	$1,953,206
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	9	5/18/2020	SUPPLEMENT FOR EXPANSION	$107,532
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	10	7/15/2020	SUPPLEMENT FOR EXPANSION	$405,310
														Subtotal = $2,466,048

Issue Date FY: 2019 ( Subtotal = $1,978,919 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	9	6/27/2019	NON-COMPETING CONTINUATION	$1,978,919
														Subtotal = $1,978,919

Issue Date FY: 2018 ( Subtotal = $2,000,794 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	003	8	6/26/2018	NON-COMPETING CONTINUATION	$2,000,794
2018	2016	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	6	10/25/2017	COMPETING CONTINUATION	$5,572
2018	2015	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	5	10/25/2017	NON-COMPETING CONTINUATION	-$280,036
2018	2015	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	5	10/26/2017	NON-COMPETING CONTINUATION	$274,464
														Subtotal = $2,000,794

Issue Date FY: 2017 ( Subtotal = $2,043,887 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN FRANCISCO	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	004	7	6/28/2017	NON-COMPETING CONTINUATION	$2,043,887
2017	2016	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	003	6	6/13/2017	COMPETING CONTINUATION	$8,973
2017	2016	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	001	6	1/23/2017	COMPETING CONTINUATION	$265,491
2017	2015	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	5	1/23/2017	NON-COMPETING CONTINUATION	-$265,491
2017	2015	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	002	5	6/13/2017	NON-COMPETING CONTINUATION	-$8,973
														Subtotal = $2,043,887

Issue Date FY: 2016 ( Subtotal = $2,113,290 )
2016	2016	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	6	6/8/2016	COMPETING CONTINUATION	$2,113,290
														Subtotal = $2,113,290

Issue Date FY: 2015 ( Subtotal = $1,703,239 )
2015	2015	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	5	6/16/2015	NON-COMPETING CONTINUATION	$1,703,239
														Subtotal = $1,703,239

Issue Date FY: 2014 ( Subtotal = $1,703,241 )
2014	2014	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	4	6/25/2014	NON-COMPETING CONTINUATION	$1,703,241
														Subtotal = $1,703,241

Issue Date FY: 2013 ( Subtotal = $1,601,045 )
2013	2013	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	3	7/8/2013	NON-COMPETING CONTINUATION	$1,601,045
														Subtotal = $1,601,045

Issue Date FY: 2012 ( Subtotal = $1,703,241 )
2012	2012	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	2	7/3/2012	NON-COMPETING CONTINUATION	$1,703,241
														Subtotal = $1,703,241

Issue Date FY: 2011 ( Subtotal = $1,738,492 )
2011	2011	UNIVERSITY OF CALIFORNIA-SAN FRANCISCO	BOX 0812	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Allergy and Infectious Diseases Research	000	1	7/13/2011	NEW	$1,738,492
														Subtotal = $1,738,492

Grand Total All Awards = $27,141,368

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Defining the Unique Properties of the Distinct Signaling Machinery Used by the TCR

Award Number: P01AI091580

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: 07/15/2011

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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