In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens

Anne M. Dickinson, Xiao Nong Wang, Lisbet Sviland, Florry A. Vyth-Dreese, Graham H. Jackson, Ton N.M. Schumacher, John B.A.G. Haanen, Tuna Mutis, Els Goulmy

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Abstract

Minor histocompatibility antigens (mHags) are immunogenic peptides from polymorphic cellular proteins that induce strong T-cell responses after human leukocyte antigen (HLA)-matched, mHag-mismatched stem-cell transplantation. mHags with broad or limited tissue expression are target antigens for graft-versus-host (GvH) and graft-versus-leukemia (GvL) reactivities. Separation of these activities is crucial for adoptive immunotherapy of leukemia without GvH disease. Therefore, using a skin-explant assay we investigated the in situ activities of cytotoxic T lymphocytes (CTLs) specific for the ubiquitously expressed mHag H-Y and for the hematopoietic-restricted mHags HA-1 and HA-2. H-Y-specific CTLs, visualized by tetrameric HLA-mHag peptide complexes, infiltrated male skin sections within 24 hours, induced severe GvH reactions of grade III-IV and produced high levels of IFN-γ. In contrast, CTLs specific for the hematopoietic system-specific mHags HA-1 and HA-2 induced no or low GvH reactions above background and produced little or no interferon-γ, unless the skin sections were preincubated with HA-1/HA-2 synthetic peptides. These results provide the first in situ dissection of GvH effects by mHag-specific CTLs and show that ubiquitously expressed mHags are the prime targets of GvH disease.

Original languageEnglish
Pages (from-to)410-414
Number of pages5
JournalNature Medicine
Volume8
Issue number4
DOIs
Publication statusPublished - 1 Jan 2002

Cite this

Dickinson, A. M., Wang, X. N., Sviland, L., Vyth-Dreese, F. A., Jackson, G. H., Schumacher, T. N. M., ... Goulmy, E. (2002). In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens. Nature Medicine, 8(4), 410-414. https://doi.org/10.1038/nm0402-410