# COPII dependent regulation of T cell alloimmunity

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $585,730

## Abstract

ABSTRACT
T cells play a central role in adaptive immune responses. They contribute to protective as well as pathogenic
processes, such as graft versus leukemia (GVL) and graft versus host disease (GVHD) respectively, after
allogeneic hematopoietic cell (allo-HCT). The molecular mechanisms underpinning the T cell alloimmunity
are not well-understood. Identification of novel molecular targets in alloreactive T cells could lead to better
harnessing of allo-HCT, a potent therapy against many hematological and inherited diseases. Naïve T cells
upon activation by allo-antigens undergo metabolic reprogramming, upregulate transcription and translation.
Following translation from mRNA, many cellular proteins egress from the endoplasmic reticulum (ER) to
Golgi bodies (ER to Golgi pathway) for appropriate post-translational modifications prior to their transport to
final intracellular location or extracellular secretion. ER to Golgi transport is mediated by the conserved Coat
Protein Complex II (COPII) vesicles. COPII vesicles are made of heterodimers of proteins, critical amongst
which are the SEC23 proteins7. The role of sec23 dependent COPII mediated ER to Golgi transport in T cell
immunity is unknown. This proposal will address the above knowledge gap. As preliminary data, we have
generated several types of novel SEC23 transgenic mice, have an IRB approved access to rare Sec23b mutated
genetic disease patient and healthy human samples for complementary murine and human studies to test the
central hypothesis that the disruption of COPII by Sec23 mutation will reduce T-cell alloimmunity in vitro and
in vivo. The Specific Aims (SA) are:
SA 1: To determine the impact of disruption of SEC23B-dependent COPII pathway in conventional donor T
cells (Tcons) on outcomes after experimental allogeneic HCT
SA 2: To determine the molecular and genetic mechanisms of SEC23 dependent COPII vesicles in regulation
of T cell functions.
Thus our thus proposal explores a heretofore unstudied pathway, role of SEC23 dependent COPII vesicles in
immunity and represents a new direction in understanding the biology, and in identification of SEC23 as a novel
therapeutic target to mitigate T cell alloreactive responses after allo-HCT. It is grounded in novel preliminary
data, will apply state of the art methods, utilize synergistic and complementary murine and human model systems,
and is supported by co-investigators with requisite expertise. If successful, will provide fundamental mechanistic
insights into T cell allo-immunity with direct implications for allo-HCT and solid organ allo-graft rejection, and
may also have broad implications for autoimmunity, infectious immunity.

## Key facts

- **NIH application ID:** 9997191
- **Project number:** 1R01HL152605-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** PAVAN REDDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $585,730
- **Award type:** 1
- **Project period:** 2020-05-10 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997191

## Citation

> US National Institutes of Health, RePORTER application 9997191, COPII dependent regulation of T cell alloimmunity (1R01HL152605-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997191. Licensed CC0.

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