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Title: Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [1];  [1];  [2];  [2];  [2];  [2];  [1];  [3]
  1. 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,
  2. 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,
  3. 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
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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.

Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1460885
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Vol. 115 Journal Issue: 31; ISSN 0027-8424
Publisher:
Proceedings of the National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 20 works
Citation information provided by
Web of Science

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