Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
The role of self-peptides in direct T cell allorecognition
Hossam A. Abdelsamed, Fadi G. Lakkis
Hossam A. Abdelsamed, Fadi G. Lakkis
Published November 1, 2021
Citation Information: J Clin Invest. 2021;131(21):e154096. https://doi.org/10.1172/JCI154096.
View: Text | PDF
Commentary Article has an altmetric score of 6

The role of self-peptides in direct T cell allorecognition

  • Text
  • PDF
Abstract

Direct allorecognition, the ability of host T cells to recognize intact allogeneic MHC molecules on transplanted tissues, is often assumed to be less dependent on the peptide bound to the MHC molecule than are other antigen recognition pathways. In this issue of the JCI, Son et al. provide unequivocal, in vivo evidence that direct allorecognition depends on the self-peptides bound to the non-self MHC molecule. The authors demonstrate that the induction of allospecific tolerance required the presentation of self-peptides by the non-self MHC molecule, and that only a handful of these peptides accounted for a sizeable proportion of the immunogenicity of the MHC antigen. These are important findings for transplant immunologists because they provide molecular insights into the biology of direct allorecognition, the prime driver of the alloimmune response to MHC-mismatched grafts, and much-needed tools, peptide–MHC multimers, to track and study polyclonal alloreactive T cells.

Authors

Hossam A. Abdelsamed, Fadi G. Lakkis

×

Figure 1

Peptide dependence of the alloimmune response.

Options: View larger image (or click on image) Download as PowerPoint
Peptide dependence of the alloimmune response.
(A) Direct and indirect a...
(A) Direct and indirect allorecognition is mediated by recipient TCRs. Direct allorecognition involves the binding of self (recipient) TCRs to non-self (donor) MHC molecules loaded with self-peptides, whereas indirect allorecognition is mediated by recipient TCRs that recognize non-self (donor) peptides bound to self (recipient) MHC molecules. (B) X-ray crystal structure binds the TCR and the peptide–MHC complex. Note that the variable domains of the TCR, Vα and Vβ, contact the peptide as well as the regions of the MHC molecule surrounding the peptide-binding groove. Figure created in Biorender. Protein Data Bank accession: 2CKB. (C) Direct T cell alloreactivity is the summation of many nondominant T cell clones (yellow), a small number of dominant T cell clones (blue), or an intermediate number of nondominant and dominant T cell clones (red). The experiments by Son et al. (16) suggest alloreactivity is the intermediate scenario (red).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 10 X users
15 readers on Mendeley
See more details