# Molecular and functional investigation of the role of CD1 in gamma delta T cell surveillance

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $599,653

## Abstract

γδ T cells constitute an important component of the immune response against infectious agents and cancerous
transformations, yet the biochemical mechanisms by which they detect antigen through their somatically
recombined T cell receptor (TCR) remain unclear. Unlike αβTCRs, which are restricted to recognizing antigens
in the context of Major Histocompatibility Complex (MHC) molecules, γδTCRs can recognize a diversity of ligands
ranging from self MHC to intact, unprocessed, viral glycoproteins. Our recent work has established CD1
molecules as ligands for a subpopulation of human Vδ1 γδ T cells, producing robust functional, biochemical and
structural evidence. We seek to extend our studies to the human gut, where γδ T cells, and in particular, Vδ1+
T cells, predominate. Our preliminary data suggests that CD1 recognition is robust and present in all individuals
examined, and that there exist important functional differences between CD1 reactive γδ T cells in tumors versus
healthy adjoining tissue. Thus, the long-term goal of this proposal is to fully characterize this CD1 reactive
population in tumors versus healthy tissue, examining their functional effector phenotypes, TCR repertoire and
immunomodulatory signals, in addition to the TCR, that shape the recruitment, activation and potential expansion
of these cells in the context of a highly relevant human disease, colorectal cancer. Our first aim,
“Characterization of CD1-specific γδ T cells in normal and diseased tissue.”, seeks to use classical cellular
expansions complemented by direct ex vivo functional and transcript analysis to profile CD1 reactive and non-
reactive T cell populations derived from tumor and adjoining healthy tissue. These data will provide insight into
the signals that regulate γδ T cells within the tumor microenvironment compared to healthy tissue. Our second
aim, “Elucidation of the molecular mechanisms by which γδ TCRs bind to CD1/lipid complexes.”, will
focus on characterizing the interaction between the γδ TCRs expressed by these cells and CD1/lipid antigen.
We will use protein biochemistry, biophysics and x-ray crystallography to elucide the molecular mechanisms by
which the γδ TCR recognizes CD1/lipid. Our effort will significantly expand our understanding of the specific
signals that regulate γδ T cell activity in human health and disease. Our third aim, “Determine the presence
and role of ligand, co-stimulatory and/or co-receptor molecules in CD1 specific γδ T cell activation and
phenotype in the colon” will characterize the ligand and immunomodulatory signals that may regulate the
activity of CD1 reactive γδ T cells in the context of human colorectal cancer. We will combine RNAseq and
differentiation assays using cord blood derived, naïve Vδ1 cells to test the relevance of candidate signals. This
will be complemented by in vitro derived native Vδ1 T cells through the OP9/DL1 system. γδ T cells can be either
pro-inflammatory or regulatory, therefore we seek to unders...

## Key facts

- **NIH application ID:** 10100415
- **Project number:** 1R01AI155984-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Erin June Adams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $599,653
- **Award type:** 1
- **Project period:** 2020-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100415

## Citation

> US National Institutes of Health, RePORTER application 10100415, Molecular and functional investigation of the role of CD1 in gamma delta T cell surveillance (1R01AI155984-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10100415. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*