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Updated: Jan 9, 2026
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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
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Control of antigen presentation on MHC-I by a bacterial secretion system
Owen Leddy1,2,3, Rachel McGinn1,2, Benjamin Allsup1,2
1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge MA USA.
Biorxiv : the Preprint Server for Biology
|December 3, 2025
Summary
Mycobacterium tuberculosis uses its ESX-1 secretion system to present bacterial antigens on MHC-I molecules, crucial for CD8 T cell recognition in tuberculosis immunity. This pathogen-driven process is key for immune response and potential therapeutic strategies.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Tuberculosis (TB) is a major global infectious disease.
- CD8 T cells are vital for controlling Mycobacterium tuberculosis (Mtb) infection.
- Mechanisms of Mtb antigen presentation on MHC-I are not fully understood.
Purpose of the Study:
- To investigate the role of Mtb secretion systems in MHC-I antigen presentation.
- To define the pathways by which Mtb antigens access the MHC-I presentation machinery.
- To explore implications for tuberculosis vaccine development.
Main Methods:
- Quantitative immunopeptidomics to identify presented Mtb peptides.
- Host and Mtb genetic manipulation to study ESX-1 secretion system function.
- T cell activation assays to assess immune responses.
- Analysis of antigen processing pathways including TAP, autophagy, and MPEG1.
Main Results:
- Mtb antigen presentation on MHC-I requires the ESX-1 type VII secretion system.
- Antigen presentation is dependent on the transporter associated with antigen processing (TAP).
- ESX-1-mediated presentation is independent of autophagy or MPEG1-mediated pore formation.
- Pathogen secretion, not non-specific membrane damage, controls MHC-I antigen access.
Conclusions:
- The ESX-1 secretion system actively drives Mtb antigen presentation on MHC-I.
- This reveals a novel secretion system-dependent mechanism for interfacing with host immunity.
- Findings may inform tuberculosis vaccine design and synthetic antigen delivery strategies.
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