DNA Barcoded Peptide-MHC Multimers to Measure and Monitor Minor Histocompatibility Antigen-specific T Cells After Allogeneic Stem Cell Transplantation

Overview

Journal J Immunother Cancer

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2024 Dec 9

PMID 39653555

Authors

Kyra J Fuchs

Marcus Goransson

Michel G D Kester

Natasja W Ettienne

Marian van de Meent

Rob C M de Jong

Eva A S Koster

Constantijn J M Halkes

Ferenc Scheeren

Mirjam H M Heemskerk

Peter van Balen

J H Frederik Falkenburg

Sine R Hadrup

Marieke Griffioen

Affiliations

Soon will be listed here.

Abstract

Allogeneic stem cell transplantation (alloSCT) provides a curative treatment option for hematological malignancies. After HLA-matched alloSCT, donor-derived T cells recognize minor histocompatibility antigens (MiHAs), which are polymorphic peptides presented by HLA on patient cells. MiHAs are absent on donor cells due to genetic differences between patient and donor. T cells targeting broadly expressed MiHAs induce graft-versus-leukemia (GvL) reactivity as well as graft-versus-host disease (GvHD), while T cells for MiHAs with restricted or preferential expression on hematopoietic or non-hematopoietic cells may skew responses toward GvL or GvHD, respectively. Besides tissue expression, overall strength of GvL and GvHD is also determined by T-cell frequencies against MiHAs.Here, we explored the use of DNA barcode-labeled peptide-MHC multimers to detect and monitor antigen-specific T cells for the recently expanded repertoire of HLA-I-restricted MiHAs. In 16 patients who experienced an immune response after donor lymphocyte infusion, variable T-cell frequencies up to 30.5% of CD8 T cells were measured for 49 MiHAs. High T-cell frequencies above 1% were measured in 12 patients for 19 MiHAs, with the majority directed against mismatched MiHAs, typically 6-8 weeks after donor lymphocyte infusion and at the onset of GvHD. The 12 patients included 9 of 10 patients with severe GvHD, 2 of 3 patients with limited GvHD and 1 of 3 patients without GvHD.In conclusion, we demonstrated that barcoded peptide-MHC multimers reliably detect and allow monitoring for MiHA-specific T cells during treatment to investigate the kinetics of immune responses and their impact on development of GvL and GvHD after HLA-matched alloSCT.

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