# CD1-restricted T-cell Responses in Skin

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $514,260

## Abstract

ABSTRACT
One crucial barrier mechanism via which the skin defends against microbial infection involves the innate
immune function of the epidermis. This function is partly mediated by Langerhans cells (LCs), which are a skin-
specific resident dendritic cell (DC) subset. We found that LCs contribute to the cutaneous immune response
to Mycobacterium leprae (mLEP, the causative agent of leprosy) via a CD1a-restricted antigen presentation
pathway to T cells, which reflects correlations with the self-limiting vs. the progressive clinical forms of leprosy .
CD1a+ LC also increase during reversal reactions (RR), when patients upgrade from the lepromatous to the
tuberculoid pole. Our findings during the past 4 years of funding reveal new paradigms: 1) autophagy links
antigen presentation to antimicrobial activity in LCs; 2) LC-intrinsic antibacterial mechanisms and mechanisms
by which CD1a-restricted T cells kill bacteria in LCs; and 3) novel evidence that CD1a-restricted T cells
recognize microbial peptides. Based on these findings, we hypothesize that CD1a-restricted presentation of
microbial peptide antigens induces T cell dependent antimicrobial pathways in infected LCs. We propose to
use leprosy as a model to examine this new concept that CD1a-restricted T cell and LC immunobiology are
linked in host defense in skin. We propose to: 1) determine intrinsic pathways by which activated LC kill
intracellular bacteria, 2) investigate the mechanisms by which CD1a-restricted T cells kill mLEP in LC; and, 3)
define mechanisms by which LC process and present CD1a-restricted bacterial peptides to T cells. These
studies are intended to provide a comprehensive and in-depth view of CD1-restricted T cell function and LC
biology in relation to a model of human skin disease, leprosy. The goal is to understand mechanisms of host
defenses against microbial pathogens in skin.

## Key facts

- **NIH application ID:** 10898869
- **Project number:** 5R01AR040312-34
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ROBERT L MODLIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $514,260
- **Award type:** 5
- **Project period:** 1991-04-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898869

## Citation

> US National Institutes of Health, RePORTER application 10898869, CD1-restricted T-cell Responses in Skin (5R01AR040312-34). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10898869. Licensed CC0.

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