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Published on: April 25, 2018
The TG2/LRP1 Pathway for T Cell Activation by Post-Translationally Modified Antigens
Agnele Sylvia Sewa1, Fu-Chen Yang2, Chaitan Khosla2,3,4
1Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
Immunological Reviews
|August 5, 2026
Summary
Post-translational modifications (PTMs) create neo-epitopes that trigger immune responses. The TG2/LRP1 pathway efficiently presents these modified peptides as T-cell antigens, offering insights into autoimmunity and vaccine design.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Post-translational modifications (PTMs) generate neo-epitopes, potentially breaking immune tolerance.
- Dietary gluten peptides modified by Transglutaminase 2 (TG2) are implicated in celiac disease.
- Efficient antigen presentation by antigen-presenting cells (APCs) is crucial for immune responses.
Purpose of the Study:
- To explore the TG2/LRP1 pathway as a novel mechanism for presenting modified peptides as T-cell antigens.
- To elucidate the role of TG2 and LRP1 in the uptake and presentation of deamidated gluten peptides.
- To discuss the implications of this pathway in autoimmunity and vaccine development.
Main Methods:
- Review of existing literature on PTMs, TG2, LRP1, and antigen presentation.
- Analysis of the molecular interactions between TG2, peptides, and LRP1.
- Discussion of the cellular mechanisms involved in antigen uptake and processing.
Main Results:
- The TG2/LRP1 pathway facilitates the efficient endocytosis of TG2-modified peptides by APCs.
- TG2-modified peptides are released as deamidated products in the endo-lysosomal compartment.
- This pathway may also be relevant for autoimmune diseases like rheumatoid arthritis involving peptidylarginine deiminase (PADI).
Conclusions:
- The TG2/LRP1 pathway represents a new paradigm for coupling PTMs with T-cell antigen presentation.
- This mechanism is critical for the immunogenicity of modified peptides, particularly in celiac disease.
- Understanding the TG2/LRP1 pathway has significant implications for autoimmune disease research and therapeutic strategies, including vaccine design.
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