# Core-002

> **NIH NIH U19** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $433,466

## Abstract

The fundamental premise of our application is to provide unbiased, non-hypothesis driven analyses of
immune signatures (IMS) associated with two important human diseases, namely dengue virus (DENV)
and Mycobacterium tuberculosis (Mtb). In the current cycle, we successfully accomplished the goals set
forth in the original proposal and have characterized memory T cell IMS associated with DENV and Mtb in
the context of: 1) natural immunity and/or control of infection, 2) active and severe disease, and 3)
administration of licensed or experimental vaccines. Our group has studied DENV and Mtb for several
years for the following reasons: 1) they are both current global health problems, 2) memory T cells are
fundamentally associated with protective immunity for these diseases, 3) antigen-specific T cell responses
are detected in sufficient numbers ex vivo, making them accessible for “omics” studies without the need for
in vitro expansion, and 4) human specimens associated with natural infection/immunity and severe disease
are easily accessible in large numbers. The HIPC study format was ideally suited to accomplish the
proposed mission. Each project and core was and remains critically dependent on other elements of the
program. In the context of HIPC, we were able to realize synergies, benefit from economies of scale, and
bring groups of investigators with different expertise together.
As a result, we developed a critical mass that is extensively leveraged in the proposed extension, based
on: 1) an established team of experienced investigators, 2) clinical collaborations with leaders in the field,
3) an extensive collection of epitopes restricted by a variety of different HLA class I and II molecules to
allow an analysis of memory T cells with unprecedented precision, 4) IMS associated with specific T cell
subsets representing key players in immunity, and 5) established “omics” assays and analysis pipelines to
generate IMS related to DENV and Mtb.
In this proposed extension, we plan to build on the definition of the T cell IMS in DENV and Mtb
accomplished in the current 5-year funding period by expanding the significance and the dimensionality of
the observations in multiple, yet related and synergistic, directions. As mentioned above, the work
performed in the current cycle identified IMS associated with specific T cell subsets in natural infection,
vaccination, and acute/severe disease. It is also clear that these T cell subsets are themselves
heterogeneous. Here, we will utilize single-cell sequencing to “drill down” and establish IMS of the specific
cell types responsible for this heterogeneity. The second dimension will “drill up” by considering additional
cell subsets. For DENV, this will be accomplished by determining the IMS of whole unfractionated PBMC
stimulated by epitopes recognized by DENV memory T cells. For Mtb, we will extend our focus to
unconventional CD4-CD8-double-negative T cells which we have found to be responsive to bacterial
lys...

## Key facts

- **NIH application ID:** 10153992
- **Project number:** 4U19AI118626-06
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Alessandro Sette
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,466
- **Award type:** 4C
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153992

## Citation

> US National Institutes of Health, RePORTER application 10153992, Core-002 (4U19AI118626-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10153992. Licensed CC0.

---

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