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Investigating commensal antigen recognition by CD8ab+ intraepithelial lymphocytes in the small intestine

Award Number: F31DK148014
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Investigating commensal antigen recognition by CD8ab+ intraepithelial lymphocytes in the small intestine - PROJECT SUMMARY Intraepithelial lymphocytes (IELs) work together with intestinal epithelial cells (IECs) to provide protection against pathogens and maintain immune tolerance in the small intestine. One subset of IELs, CD8αβ+ TCRαβ+ IELs, are antigen-experienced T cells that have been studied during intestinal infections. However, these cells are present in mice in the absence of infection and their numbers are reduced in germ-free mice, indicating that CD8αβ+ IEL T cells may also recognize and respond to commensal bacteria. Previous work in our lab has shown that Segmented Filamentous Bacteria (SFB) promotes the accumulation of CD8αβ+ IEL T cells, but the mechanism is unknown. This project aims to elucidate the mechanism by which commensal bacteria induce the development of CD8αβ+ IEL T cells. We hypothesize that CD8αβ+ IEL T cells can recognize SFB antigens presented on IECs. In Aim 1, we will identify commensal antigen-specific CD8αβ+ IEL T cells first by identifying TCR Vβ expression enrichment on cells that have migrated to the intestinal epithelium compared to CD8αβ+ T cells in secondary lymphoid organs such as the mesenteric lymph nodes and the spleen. Preliminary experiments suggest there is an enrichment of Vβ5+ T cells in the CD8αβ+ IEL T cell population in SFB+ mice. To determine if the CD8αβ+ IEL T cells are specific for SFB, we will extract IEL T cells from Nur77-GFP mice, which help identify TCR stimulation. We will then co-culture them with SFB and dendritic cells from wild-type mice. In Aim 2, we will determine if antigen uptake, processing and presentation by IECs to CD8αβ+ IELs is necessary for their development. First, we will use mice deficient in beta-2-microblobulin in intestinal epithelial cells to assess if MHC class I expression on IECs is needed to present antigen to CD8αβ+ IEL T cells. Additionally, using different knockout mice lacking important molecules in the antigen processing machinery and in vitro antigen presentation assays, we will determine the molecular pathways in intestinal epithelial cells that are involved in commensal antigen uptake and processing to present to CD8αβ+ IEL T cells. This research will provide deeper insight into how IELs respond to commensal bacteria in the intestine, and the roles that IECs play in CD8αβ+ IEL development.


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 = $50,114 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	6/23/2026	NEW	$0
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/23/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Investigating commensal antigen recognition by CD8ab+ intraepithelial lymphocytes in the small intestine

Award Number: F31DK148014

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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