Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro
Abstract
Significance T cells recognize their targets through the T cell receptor (TCR). The affinity of a typical receptor for an agonist peptide-major histocompatibility complex (pMHC) molecule is extremely weak, and TCRs are known to be cross-reactive for related peptides. However, there are known TCR/pMHC interactions that occur at weaker affinities, such as in thymic selection and recognition of self-antigens, yet little is known about the identity of these peptides. We show that TCR/pMHC interactions of extremely low affinities remain highly specific, which informs of the nature of extremely weak affinity ligands. We also show that a peptide “velcro” can induce peptide-dependent T cell activation, providing a method for increasing the potency of a target, which is useful in immunotherapy.
- Authors:
-
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305,, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305,, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305,
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305,, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305,
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305,, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305,, Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305,, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1460885
- Grant/Contract Number:
- AC02-76SF00515
- Resource Type:
- Published Article
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 31; Journal ID: ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of Sciences
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Gee, Marvin H., Sibener, Leah V., Birnbaum, Michael E., Jude, Kevin M., Yang, Xinbo, Fernandes, Ricardo A., Mendoza, Juan L., Glassman, Caleb R., and Garcia, K. Christopher. Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro. United States: N. p., 2018.
Web. doi:10.1073/pnas.1802746115.
Gee, Marvin H., Sibener, Leah V., Birnbaum, Michael E., Jude, Kevin M., Yang, Xinbo, Fernandes, Ricardo A., Mendoza, Juan L., Glassman, Caleb R., & Garcia, K. Christopher. Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro. United States. https://doi.org/10.1073/pnas.1802746115
Gee, Marvin H., Sibener, Leah V., Birnbaum, Michael E., Jude, Kevin M., Yang, Xinbo, Fernandes, Ricardo A., Mendoza, Juan L., Glassman, Caleb R., and Garcia, K. Christopher. Wed .
"Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro". United States. https://doi.org/10.1073/pnas.1802746115.
@article{osti_1460885,
title = {Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro},
author = {Gee, Marvin H. and Sibener, Leah V. and Birnbaum, Michael E. and Jude, Kevin M. and Yang, Xinbo and Fernandes, Ricardo A. and Mendoza, Juan L. and Glassman, Caleb R. and Garcia, K. Christopher},
abstractNote = {Significance T cells recognize their targets through the T cell receptor (TCR). The affinity of a typical receptor for an agonist peptide-major histocompatibility complex (pMHC) molecule is extremely weak, and TCRs are known to be cross-reactive for related peptides. However, there are known TCR/pMHC interactions that occur at weaker affinities, such as in thymic selection and recognition of self-antigens, yet little is known about the identity of these peptides. We show that TCR/pMHC interactions of extremely low affinities remain highly specific, which informs of the nature of extremely weak affinity ligands. We also show that a peptide “velcro” can induce peptide-dependent T cell activation, providing a method for increasing the potency of a target, which is useful in immunotherapy.},
doi = {10.1073/pnas.1802746115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 31,
volume = 115,
place = {United States},
year = {2018},
month = {7}
}
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https://doi.org/10.1073/pnas.1802746115
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