PMID- 11927949
OWN - NLM
STAT- MEDLINE
DCOM- 20020502
LR  - 20141120
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 8
IP  - 4
DP  - 2002 Apr
TI  - In situ dissection of the graft-versus-host activities of cytotoxic T cells 
      specific for minor histocompatibility antigens.
PG  - 410-4
AB  - 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.
FAU - Dickinson, Anne M
AU  - Dickinson AM
AD  - University Department of Haematology, Royal Victoria Infirmary, University of 
      Newcastle, Newcastle upon Tyne, UK.
FAU - Wang, Xiao-Nong
AU  - Wang XN
FAU - Sviland, Lisbet
AU  - Sviland L
FAU - Vyth-Dreese, Florry A
AU  - Vyth-Dreese FA
FAU - Jackson, Graham H
AU  - Jackson GH
FAU - Schumacher, Ton N M
AU  - Schumacher TN
FAU - Haanen, John B A G
AU  - Haanen JB
FAU - Mutis, Tuna
AU  - Mutis T
FAU - Goulmy, Els
AU  - Goulmy E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (H-Y Antigen)
RN  - 0 (HA-1 antigen)
RN  - 0 (HA-2 antigen)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Oligopeptides)
SB  - IM
MH  - Graft vs Host Disease/etiology/immunology/pathology
MH  - Graft vs Host Reaction/*immunology
MH  - H-Y Antigen/metabolism
MH  - Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Humans
MH  - In Vitro Techniques
MH  - Minor Histocompatibility Antigens/*metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Oligopeptides/metabolism
MH  - Skin/immunology/pathology
MH  - T-Lymphocytes, Cytotoxic/*immunology/pathology
EDAT- 2002/04/03 10:00
MHDA- 2002/05/03 10:01
CRDT- 2002/04/03 10:00
PHST- 2002/04/03 10:00 [pubmed]
PHST- 2002/05/03 10:01 [medline]
PHST- 2002/04/03 10:00 [entrez]
AID - nm0402-410 [pii]
AID - 10.1038/nm0402-410 [doi]
PST - ppublish
SO  - Nat Med. 2002 Apr;8(4):410-4. doi: 10.1038/nm0402-410.