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Expression of gamma delta TCR ligands in development

Award Number: R21AI129401
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: 02/07/2017
PERIOD OF PERFORMANCE END DATE: 05/31/2019

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Expression of gamma delta TCR ligands in development - Individual TCR γ and δ genes are rearranged and expressed in a series of overlapping waves during murine development with cells bearing specific TCR preferentially or exclusively migrating from the thymus to specific epithelial and lymphoid sites. γδ T cells that rearrange their TCR during early fetal development express highly restricted or invariant TCR. The first TCR-bearing cells migrate from the developing thymus to the skin where they take up residence in the epidermis as Thy-1+ dendritic epidermal T cells (DETC). Similarly, subsequent waves of γδ TCR expressing thymocytes migrate to other epithelial tissues. The presence of these γδ T cell populations with restricted TCR use in distinct epithelial locations supports recognition of unique, tissue- specific antigens and specialized functions for these cells. However, roles for TCR signals in development and ligands for these invariant γδ TCRs are currently poorly understood. We hypothesize that novel endogenous Vγ3Vδ1 TCR ligands are expressed in the embryonic thymus and deliver key signals for DETC precursor development and that expression of these ligands is upregulated on skin epithelial cells following stress and functions to deliver activation signals to DETC following injury or stress. We have developed tools for detection of Vγ3Vδ1 TCR ligands and found expression on embryonic, but not adult, thymic epithelial cells. Based upon these results, we are now in a position to identify and characterize this fetal TCR ligand and determine its role in DETC precursor development and activation of DETC function.


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: 2020 ( Subtotal = $0 )
2020	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	11/4/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $240,625 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	1/29/2018	NON-COMPETING CONTINUATION	$240,625
														Subtotal = $240,625

Issue Date FY: 2017 ( Subtotal = $288,750 )
2017	2017	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	2/7/2017	NEW	$288,750
														Subtotal = $288,750

Grand Total All Awards = $529,375

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Expression of gamma delta TCR ligands in development

Award Number: R21AI129401

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: 02/07/2017

PERIOD OF PERFORMANCE END DATE: 05/31/2019

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