T-cell receptor repertoires against HLA class I-restricted minor histocompatibility antigens are highly diverse with a small subset of public clonotypes.

Authors

Kyra J Fuchs, Marian van de Meent, Michel G D Kester, Renate S Hagedoorn, Indu Khatri, Peter van Balen, Mirjam H M Heemskerk, Erik B van den Akker, J H Frederik Falkenburg, Marieke Griffioen

Published in

Journal for immunotherapy of cancer. Volume 14. Issue 8. Aug 20, 2026. Epub Aug 20, 2026.

Abstract

Allogeneic hematopoietic stem cell transplantation (alloHSCT) can be a curative treatment for hematological diseases. After HLA-matched alloHSCT, donor T cells may recognize minor histocompatibility antigens (MiHAs), which are polymorphic HLA-binding peptides on patient cells that are absent from donor cells due to genetic differences. Donor T cells can induce beneficial anti-tumor effects if MiHAs are targeted on malignant hematopoietic cells in the patient, while graft-versus-host disease (GvHD) may develop if MiHAs are targeted on patients' healthy non-hematopoietic tissues.
We previously isolated T-cell clones from patients responding to donor lymphocyte infusions (DLIs) after HLA-matched alloHSCT, and identified HLA class I-restricted MiHAs. To investigate MiHA-specific T-cell responses in patients, we here sequenced the T-cell receptors (TCRs) of MiHA-specific T-cell clones and identified 394 distinct TCRs against 122 MiHAs. We used the collection of identified TCRs to measure frequencies of matched MiHA-specific TCRs in 39 patients responding to DLI with antitumor responses accompanied with no (n=9), limited (n=8) or severe (n=22) GvHD.
The data showed higher MiHA-specific TCR frequencies in patients with severe GvHD, which were mainly driven by clonal expansion. Moreover, within the diverse MiHA-specific TCR repertoires in these patients, we identified five public TCRs against four MiHAs with identical CDR3 regions and several TCRs targeting MiHAs with similar, but not identical, CDR3 regions.
Patients with severe GvHD have high MiHA-TCR frequencies mainly driven by clonal expansion, and that MiHA-specific TCR repertoires in patients responding to DLI after alloHSCT are highly diverse with a few public clonotypes.

PMID:
42624530
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.