PMID- 20802400
OWN - NLM
STAT- MEDLINE
DCOM- 20101124
LR  - 20101101
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 90
IP  - 9
DP  - 2010 Nov 15
TI  - Identification of MHC II-restricted minor histocompatibility antigens after 
      HLA-identical stem-cell transplantation.
PG  - 1030-5
LID - 10.1097/TP.0b013e3181f5470c [doi]
AB  - BACKGROUND: After allogeneic hematopoietic stem-cell transplantation (HSCT), 
      donor-derived T cells may elicit graft-versus-host disease (GVHD) and 
      graft-versus-tumor (GVT) responses. The main targets of GVHD and GVT responses 
      after human leukocyte antigen (HLA)-identical HSCT are minor histocompatibility 
      antigens (mHAgs), that is, polymorphic gene products in which recipient and donor 
      differ. Thus, for increasing beneficial GVT and decreasing life-threatening GVHD 
      responses, knowledge of the relevant mHags is required. Here, we sought to 
      identify mHags recognized by CD4 T cells using a novel serologic approach. 
      METHODS: To identify candidate mHAgs recognized by CD4 T cells, a cDNA expression 
      library from peripheral blood mononuclear cells of a patient with beta-thalassemia 
      major was screened with serum taken at different time points after HLA-identical 
      HSCT. RESULTS: Immune responses against 18 antigens were identified with serum 
      taken 100 days posttransplantation, when the patients had recovered from acute 
      GVHD II. Except for one, no humoral responses against these antigens were 
      detected 25 days or 1 year after transplantation. Sequence comparison of these 
      antigens between recipient and donor revealed three polymorphisms of which two 
      were contained within epitopes predicted to bind to HLA-DR molecules of the 
      patient. Using cytokine secretion and capture assays, T cells specific for the 
      polymorphic antigens of the recipient, but not the donor, were isolated from 
      peripheral blood monocyte cells after HSCT. CONCLUSIONS: The serologic approach 
      described here facilitates the rapid identification of mHAgs recognized by CD4 T 
      cells. Furthermore, the correlation of humoral and cellular immune responses with 
      acute GVHD implies a role of these antigens in GVHD pathology.
FAU - Milosevic, Slavoljub
AU  - Milosevic S
AD  - Clinical Cooperation Group, Helmholtz-Zentrum Munchen, Munich, Germany.
FAU - Bachnick, Barbara
AU  - Bachnick B
FAU - Karim, Karzan
AU  - Karim K
FAU - Bornkamm, Georg W
AU  - Bornkamm GW
FAU - Witter, Klaus
AU  - Witter K
FAU - Gerbitz, Armin
AU  - Gerbitz A
FAU - Mautner, Josef
AU  - Mautner J
FAU - Behrends, Uta
AU  - Behrends U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Minor Histocompatibility Antigens)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Graft vs Host Disease/immunology
MH  - HLA Antigens/genetics/immunology
MH  - Histocompatibility Antigens Class II/genetics/immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - Minor Histocompatibility Antigens/*immunology
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single Nucleotide
MH  - *Stem Cell Transplantation
MH  - Tissue Donors
MH  - Transplantation, Homologous/immunology
EDAT- 2010/08/31 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/08/31 06:00
PHST- 2010/08/31 06:00 [entrez]
PHST- 2010/08/31 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - 10.1097/TP.0b013e3181f5470c [doi]
PST - ppublish
SO  - Transplantation. 2010 Nov 15;90(9):1030-5. doi: 10.1097/TP.0b013e3181f5470c.