# Regulation of T Cell Responses by Chaperone-Mediated Autophagy

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $417,500

## Abstract

Abstract
T cell activation requires a tight regulation of positive and negative modulators of signaling pathways
downstream of the T cell receptor (TCR). Degradation of specific proteins following TCR engagement is an
essential regulatory mechanism that ensures efficient T cell responses. Chaperone-mediated autophagy (CMA)
is an inducible form of autophagy that selectively degrades soluble cytosolic proteins that present a pentapetide
targeting motif. The ability of CMA to selectively degrade proteins makes this type of autophagy a candidate to
contribute to the regulation of the levels of specific signaling intermediates in response to different stimuli. We
have recently shown that CMA is activated in CD4+ T cells in response to TCR engagement to regulate signaling
pathways downstream of the TCR by selectively targeting inhibitors of TCR signaling for degradation in the
lysosomes. In this proposal we intend to elucidate the molecular mechanisms that explain how this specific form
of autophagy modulates CD4+ T cell function and characterize how CMA regulates adaptive immune responses
in vivo. Our overall goal is to define CMA as a novel regulatory mechanism of T cell activation and to determine
the possibility of targeting CMA to modulate T cell responses.

## Key facts

- **NIH application ID:** 9935009
- **Project number:** 5R01AI113919-06
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Fernando Macian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,500
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935009

## Citation

> US National Institutes of Health, RePORTER application 9935009, Regulation of T Cell Responses by Chaperone-Mediated Autophagy (5R01AI113919-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9935009. Licensed CC0.

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