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

Nat Med. 2002 Apr;8(4):410-4. doi: 10.1038/nm0402-410.


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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Graft vs Host Reaction / immunology*
  • H-Y Antigen / metabolism
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • In Vitro Techniques
  • Minor Histocompatibility Antigens / metabolism*
  • Neoplasm Proteins / metabolism
  • Oligopeptides / metabolism
  • Skin / immunology
  • Skin / pathology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / pathology


  • H-Y Antigen
  • HA-1 antigen
  • HA-2 antigen
  • Minor Histocompatibility Antigens
  • Neoplasm Proteins
  • Oligopeptides