Peptide mimotopes alter T cell function in cancer and autoimmunity
Jill E Slansky1, Maki Nakayama2
1Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E. 19thAvenue, Aurora, CO 80045, USA.
Seminars in Immunology
|March 25, 2020
Summary
Altering T cell epitopes with amino acid substitutions can enhance cancer and autoimmunity immunotherapies. Effective substitutions strengthen binding to T cell receptors and MHC molecules, improving treatment outcomes.
Area of Science:
- Immunology
- Oncology
- Autoimmunity
Background:
- T cells play a crucial role in recognizing self antigens in both cancer and autoimmune diseases.
- Modulating T cell responses is a key strategy for developing effective immunotherapies.
Purpose of the Study:
- To re-evaluate the strategy of using amino acid substitutions in T cell epitopes.
- To enhance the efficacy of checkpoint blockade therapies in cancer and antigen-specific immunotherapies in autoimmunity.
Main Methods:
- Analyzing how amino acid substitutions alter interactions between epitopes, MHC molecules, and T cell receptors.
- Investigating the impact of these substitutions on the T cell repertoire.
Main Results:
- Amino acid substitutions can be designed to increase binding affinity to T cell receptor (TCR) and/or MHC molecules.
- Effective substitutions lead to cross-reactivity with the same T cell repertoire as the natural antigen.
Conclusions:
- Strategic amino acid substitutions in T cell epitopes offer a promising approach to improve cancer and autoimmunity immunotherapies.
- Optimized substitutions enhance therapeutic efficacy by improving molecular interactions and maintaining T cell repertoire recognition.
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