# Maternal T cell recognition of placental antigen

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $200,880

## Abstract

Project summary. The placenta sheds a vast amount of “foreign” protein into maternal circulation during
pregnancy, to be taken up and presented by maternal antigen presenting cells (APCs). Remarkably, the
ensuing T cell response is neither immunogenic nor tolerogenic as pregnant mice neither become immunized
to the antigen (Ag), even when given strong adjuvants and depleted of regulatory T cells, nor do they become
tolerized to it. Thus, placental Ag is best considered “non-immunogenic,” a potentially unique category without
clear physiological antecedent. The objectives of this proposal are to elucidate the cellular and molecular basis
for why placental Ag is non-immunogenic. This question is central to understanding how the placenta and fetus
avoid immune rejection, and is also relevant to peripheral immune tolerance in general. As such it aligns
perfectly with the long-term goal of Dr. Rizzuto which is to understand the immune pathogenesis of pregnancy
complications and develop new therapies for use in transplantation, tumor immunology, and autoimmunity. The
overall hypothesis of the proposal is that the non-immunogenicity of placental Ag can be explained by its
physical/biochemical properties and/or the phenotype of the maternal APC, and has three specific aims.
In Aim 1, Dr. Rizzuto will investigate the Ag presentation pathways governing CD4+ T cell responses and
determine why these are non-immunogenic. This Aim builds upon preliminary data that B cells rather than
DCs are critical for presenting placental Ag to maternal CD4+ T cells. In Aim 2, she will define the
physical/biochemical properties of placental Ag that render it non-immunogenic, including exploring the
functional significance of her finding that the Ag accumulates maternal antibodies. In Aim 3, she will define
the Ag cross-presentation pathways that govern CD8+ T cell responses and determine why these are non-
immunogenic. This Aim focuses on the classical Batf3-dependent DC subset known to cross-present Ag, as
well as a currently undefined, and atypical APC. This work is relevant to the mission of NIAID because it will
significantly expand the understanding of peripheral immune tolerance mechanisms.
 Dr. Rizzuto is an MD PhD research fellow at the University of California, San Francisco. She completed
graduate work in tumor immunology and clinical training in anatomic pathology and is applying for a Mentored
Clinical Scientist Research Career Development Award (K08). Her training plan will foster the attainment of her
goal of becoming an academic physician scientist. This plan includes mentorship by Dr. Adrian Erlebacher, a
leading expert in the field of reproductive immunology; scientific and career advisory by a multidisciplinary
committee that includes leaders in the fields of immune tolerance and placental biology; coursework in
reproduction, proteomics, and biostatistics; attendance at meetings to foster collaboration; and career
development activities. These activities w...

## Key facts

- **NIH application ID:** 10071126
- **Project number:** 5K08AI137209-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Gabrielle A Rizzuto
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $200,880
- **Award type:** 5
- **Project period:** 2018-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071126

## Citation

> US National Institutes of Health, RePORTER application 10071126, Maternal T cell recognition of placental antigen (5K08AI137209-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10071126. Licensed CC0.

---

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