# Novel role of DC1 in vaccine induced CD8 T cell responses

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $201,250

## Abstract

Project Summary
The development of vaccines that can specifically generate cell mediated immunity has remained a major
challenge in the field of vaccinology for both microbial pathogens and cancer. Prior work has shown that
the use of replication deficient live microbes is one way to generate a potent pathogen-specific CD8+ T cell
response. For example, even a single low dose of the non-replicating vaccine CPS strain of Toxoplasma
gondii elicits a robust parasite specific CD8+ T cell response that provides long-lived protective immunity.
However, many questions remain about how the immune system recognizes and processes the antigens
from these attenuated organisms to prime and expand parasite-specific T cells. Prior work has shown that
the CD8+ T cell response is dependent on the Batf3-dependent dendritic cells (DC1), which are commonly
involved in antigen cross-presentation to CD8+ T cells as well as IL-12 production. Paradoxically,
preliminary data indicates that DC1 are not required for early CD8+ T cell priming, but are required to
generate a protective CD8+ T cell response. Importantly, the loss of the autophagy pathway in DC also
results in a failure to generate protective CD8+ T cells. These studies emphasize two important questions:
1) what priming-independent role do DC1 play in generating a CD8+ T cell response, 2) what autophagy-
dependent pathway in DC1 is required for the expansion and differentiation of CD8+ T cells? The
autophagy pathway has been implicated as being required for leukocyte survival in inflammatory setting as
well as an alternative pathway for the processing and presentation of parasite antigen. The studies
proposed here will use a variety of unique microbial tools (fluorescent reporters, parasite auxotrophs, Cre-
exressing parasites) and mouse strains (Batf3-/-, unique reporters, and mice which do not express MHCI H-
2Kb on DC1) combined with our imaging expertise to address I. Do DC1 interact directly with parasite-
specific CD8+ T cells in a peptide-MHCI dependent fashion to provide the signals required for T cell
expansion and differentiation and II. What autophagy-dependent processes in DC1 are required for the
generation of protective effector CD8+ T cells.

## Key facts

- **NIH application ID:** 9844444
- **Project number:** 5R21AI139895-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** CHRISTOPHER A HUNTER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2019-01-04 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844444

## Citation

> US National Institutes of Health, RePORTER application 9844444, Novel role of DC1 in vaccine induced CD8 T cell responses (5R21AI139895-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9844444. Licensed CC0.

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