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Impact of T cell receptor signaling on memory CD8+ T cell stemness

Award Number: F31AI172421
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Impact of T cell receptor signaling on memory CD8+ T cell stemness - ABSTRACT CD8+ T cells' unique ability to sense and kill pathogen-infected and tumor cells makes developing human vaccines designed to induce potent CD8+ T cell memory an important necessity. In this proposal, we explore the roles of T cell receptor (TCR) signaling and peptide/MHC (pMHC) stability on generating memory CD8+ T cells. Strong cognate antigen interactions induce robust primary effector responses and generate larger pools of memory CD8+ T cells. However, whether the quality of TCR signaling and pMHC interactions can imprint distinct CD8+ T cell memory programs is not well known. Prior studies state that differences in antigen stimulation do not lead to functional differences, but our preliminary data suggest that the strength and the stability of pMHC and TCR interactions do imprint functionally distinct cellular programs in resulting memory CD8+ T cells. Using high-dimensional spectral flow cytometry, transgenic TCR and fluorescent reporter mouse models, and an inducible lentiviral-based T cell gene editing approach, we will determine whether model epitopes with distinct TCR signaling qualities can imprint distinct memory cell programs. In addition, we will characterize a subset of memory CD8+ T cells that we propose are precursors to long-lived memory and test whether these cells confer improved pathogen-specific protection. I am confident that I will successfully execute the proposed research and training plans under the mentorship of Dr. Gregoire Lauvau with the support of our collaborators, Drs. Wenjun Guo and Fabien Delahaye, experts in stem cell transduction and computational genomics, respectively. Findings from our proposed study will contribute to a better understanding of memory CD8+ T cell formation and improve rational design for CD8+ T cell-based vaccines and adoptive T cell transfer immunotherapies.


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 = $54,538 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	3	8/6/2025	NON-COMPETING CONTINUATION	$54,538
														Subtotal = $54,538

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	2	6/13/2024	NON-COMPETING CONTINUATION	$53,974
														Subtotal = $53,974

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	002	1	6/14/2023	NEW	$0
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	003	1	7/24/2023	NEW	$5,000
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	001	1	6/14/2023	NEW	$0
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	1	6/14/2023	NEW	$47,694
														Subtotal = $52,694

Grand Total All Awards = $161,206

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Impact of T cell receptor signaling on memory CD8+ T cell stemness

Award Number: F31AI172421

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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