# Cooperation between lymphatic stroma and hematopoietic cells shapes protective immunity

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $26,594

## Abstract

Project summary:
We and others have demonstrated that antigens derived from infectious viral infections persist in the host for
extended periods of time, well beyond the time in which the infection is cleared from the host. Our lab has
specifically identified that antigens derived from both vaccination and viral infections persist or are archived by
the host lymphatic endothelial cells (LEC)s, identifying the source of archived antigens. We have published
that this archived antigen maintains a more effector like pool of antigen specific memory cells which enhances
the clearance of a secondary infectious challenge. Identification of key mechanisms involved in antigen
archiving during vaccination is critical for our understanding of enhanced protective immunity to vaccination.
While we have established many important criteria for antigen archiving and protective immunity, in this
renewal application we aim to dive deeper into the cell types involved and the processes required. We aim to
better appreciate how the expression of subset specific genes, now discovered in both lymphatic endothelial
cells and dendritic cells, may be required for antigen handling, the implications of which could affect antigen
archiving and protective immunity. We have established a novel methodology leveraging the 10x genomics
platform to identify DNA-antigen conjugates for the study of antigen dispersal over long periods of time. With
this methodology and technology in hand we now have the capability to accurately and faithfully measure cell
types that acquire antigens as well as the exact number of antigens within each cell over time. Using these
studies we have identified several novel findings based on antigen amount and transcriptional signature to lead
us to the hypothesis that specific LECs and DCs, based on their transcriptional program, contribute to the
acquisition, retention and exchange of antigens. Furthermore, this handling of antigens by LECs and DCs can
be manipulated by other inflammatory events that cause antigen release and presentation, and as a result,
improve immune responses to secondary and heterologous infections.

## Key facts

- **NIH application ID:** 10724082
- **Project number:** 3R01AI121209-06A1S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Beth Ann Tamburini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $26,594
- **Award type:** 3
- **Project period:** 2022-12-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10724082

## Citation

> US National Institutes of Health, RePORTER application 10724082, Cooperation between lymphatic stroma and hematopoietic cells shapes protective immunity (3R01AI121209-06A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10724082. Licensed CC0.

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