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Lipidomic discovery of physiological CD1 antigens and blockers for human T cells

Award Number: R01AI189471
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: 04/09/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Lipidomic discovery of physiological CD1 antigens and blockers for human T cells - Modified Project Summary/Abstract Section T cells control immune response during vaccination, autoimmunity and infection based on their recognition of antigens. This R01 resubmission proposal studies lipid antigens for T cells by taking advantage of a sensitive lipidomics platform that can comprehensively detect lipids bound to CD1 antigen presenting molecules. By detecting hundreds of lipids bound to human CD1a, CD1b, CD1c and CD1d, we will determine the general patterns of lipid capture by cellular CD1 proteins. By separating CD1 proteins that do and do not bind to T cell receptors, lipidome-scale experiments will identify chemical patterns in natural lipids that lead to activation and blockade of T cell response. Based on a prior program that identified CD1a ligands that block T cell response in vivo, we will determine the structures of CD1b, CD1c and CD1d ligands that are inhibitors for T cells. Finally, optimized blockers will be tested ex vivo using polyclonal human T cells and CD1 tetramers, with an emphasis on CD1a and CD1c blockers. Overall, we seek to develop anti-inflammatory therapies that can act through specific blockade of human T cells. Unlike the MHC antigen presenting molecules, CD1 proteins are non-polymorphic, meaning that once the CD1-lipid binding patterns are described, they will apply to nearly all humans.


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: 2026 ( Subtotal = $893,459 )
2026	2026	BRIGHAM & WOMENS HOSPITAL INC	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	4/9/2026	NEW	$893,459
														Subtotal = $893,459

Grand Total All Awards = $893,459

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Lipidomic discovery of physiological CD1 antigens and blockers for human T cells

Award Number: R01AI189471

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: 04/09/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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