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Lookup NU author(s): Professor Anne Dickinson,
Dr Xiao WangORCiD
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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(1,2). mHags with broad or limited tissue expression are target antigens for graft-versus-host (GvH) and graft-versus-leukemia (GvL) reactivities(1). 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(3), infiltrated male skin sections within 24 hours, induced severe GvH reactions of grade III-IV and produced high levels of IFN-gamma. 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-gamma, 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.
Author(s): Dickinson AM; Wang XN; Sviland L; Vyth-Dreese FA; Jackson GH; Schumacher TNM; Haanen JBAG; Mutis T; Goulmy E
Publication type: Article
Publication status: Published
Journal: Nature Medicine
ISSN (print): 1078-8956
ISSN (electronic): 1546-170X
Publisher: Nature Publishing Group
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