# The Function of MHC Class II on Lung Type II Alveolar Cells

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2021 · $8,265

## Abstract

Project Summary: Lower respiratory tract infections are a leading cause of death worldwide. Current vaccines
and targeted treatments for such infections, including lung viral infections in particular, are sparse and poorly
efficacious. Thus, there is a critical need to improve our understanding of antiviral immune responses in the
lung. Morbidity from lung viral infections results from both virus-induced and immune-mediated lung damage,
and adaptive immune cells influence both of these processes; they are required for viral clearance, but they
are also a main cause of lung immunopathology. The mechanisms that regulate the balance between these
protective and pathologic responses are poorly understood. The purpose of this proposal is to provide insight
into how antiviral and immunopathologic functions are regulated in the lung parenchyma.
 We have recently identified type II alveolar cells (AT2) as important regulators of immune responses to
lung viral infections. AT2 are abundant epithelial cells present in the distal lung, and unlike most other
nonhematopoietic cells, they constitutively express MHC class II (MHCII). AT2 MHCII seems to play an
important protective role in the lung, as loss of MHCII on AT2 results in significantly higher morbidity and
impaired recovery from influenza (flu) infection in mice. However, unexpectedly, AT2 do not efficiently present
antigenic peptides via MHCII. Together this suggests that during viral infection, AT2 MHCII exhibits an active
protective function and furthermore that AT2 are prevented from stimulating CD4+ T cells in the lung via MHCII.
The experiments outlined in this proposal will elucidate the mechanisms underlying AT2 MHCII protection from
flu disease as well as those limiting AT2 MHCII presentation to CD4+ T cells.
 Aim 1 will investigate the factors contributing to AT2 MHCII-mediated protection during flu infections by
comparing flu-infected mice with and without AT2 MHCII and evaluating the effect of CD8+ T cell depletion, the
phenotype and function of lung-infiltrating immune cells, virus titers, and lung pathology. Aim 2 will assess the
mechanisms that limit AT2 MHCII antigen presentation, in particular evaluating the role of the canonical MHCII
processing chaperones invariant chain and H2M in restricting AT2 MHCII presentation.
 These experiments will be complemented by a rigorous training plan focused on achieving my scientific,
clinical, and professional goals. Specifically, this plan involves improving my knowledge of advanced laboratory
techniques, ability to critically evaluate scientific work, and communication with collaborators and fellow
scientists. Additionally, it includes strategies for refining my teaching, leadership, and patient care skills. My
training will take place at the University of Pennsylvania, a research institution rich with diverse scientific
resources and a highly collaborative atmosphere, under the guidance of the Medical Scientist Training
Program as well as my Ph...

## Key facts

- **NIH application ID:** 10383127
- **Project number:** 5F30HL145907-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Sushila Toulmin
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $8,265
- **Award type:** 5
- **Project period:** 2020-04-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10383127

## Citation

> US National Institutes of Health, RePORTER application 10383127, The Function of MHC Class II on Lung Type II Alveolar Cells (5F30HL145907-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10383127. Licensed CC0.

---

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