# Innate Immune Receptors that Promote RBC Alloimmunization

> **NIH NIH P01** · UNIVERSITY OF VIRGINIA · 2020 · $434,438

## Abstract

Summary Project 3
Significance: Red blood cell (RBC) transfusion is a powerful therapeutic tool. Despite ABO and Rh(D)
matching, leukoreduced RBCs can lead to the induction of recipient alloantibodies against minor antigens;
such antibodies may result in delay locating compatible RBC units for therapy, hemolytic transfusion reactions
or hemolytic disease of the newborn. Although there have been significant advances in our understanding of
the basic rules that govern the induction of adaptive immunity to pathogens and even transplantation, what
immunologically determines when someone will respond to an allogeneic unit of RBCs remains largely
undefined. Consequently, we cannot predict which transfusion recipients will develop alloantibodies. Identifying
the innate immune cells and receptors that regulate immunization to foreign antigens on RBCs will enable us to
identify potential immune triggers of alloimmunization during transfusion and, as an extension, targets to inhibit
during these therapies to promote immunological tolerance.
Innovation: We have developed a murine model system in which we can evaluate the role of particular innate
immune stimuli and cells during allogeneic red blood cell transfusion. These models allow us for the first time
to dissect the specific receptors and pathways required for the generation of detrimental alloimmunity during
transfusion. Our preliminary data strongly suggest that classic sensors of pathogens, the Toll-like receptors
(TLRs), also respond to transfused RBCs and instruct the activation of T and B cells to RBC-derived antigens.
Approach/Investigators: Using these murine models we will test the hypothesis that T cell priming to RBC
alloantigens is defective in the absence of innate immune pathways by eliminating combinations of
downstream signaling pathways or particular surface receptors. Dr. Eisenbarth has extensive experience in
evaluating the role of innate immune receptors in shaping T cell responses. Dr. Hendrickson is a leader in the
RBC alloimmunization field and has developed many of the widely used murine models to study this process.
In collaboration, we will address the following specific aims: Aim 1, Determine the mechanism by which MyD88
regulates adaptive immunity to allogeneic RBCs and Aim 2, Identify which Toll-like receptor(s) drive T cell-
dependent RBC alloimmunization.

## Key facts

- **NIH application ID:** 10018092
- **Project number:** 5P01HL132819-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Stephanie Caroline Eisenbarth
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,438
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018092

## Citation

> US National Institutes of Health, RePORTER application 10018092, Innate Immune Receptors that Promote RBC Alloimmunization (5P01HL132819-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018092. Licensed CC0.

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