PMID- 30681727
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20200219
IS  - 1537-2995 (Electronic)
IS  - 0041-1132 (Print)
IS  - 0041-1132 (Linking)
VI  - 59
IP  - 2
DP  - 2019 Feb
TI  - Alloimmunogenicity of an isolated MHC allele is affected by the context of MHC 
      mismatch in a murine model.
PG  - 744-753
LID - 10.1111/trf.15109 [doi]
AB  - BACKGROUND: Humoral alloimmunization to human leukocyte antigen (HLA) can 
      represent a barrier to solid-organ transplantation, can lead to a refractory 
      state in patients requiring platelet transfusion, and can also contribute to 
      transfusion-related acute lung injury (TRALI). While exposure to HLA-mismatched 
      cells/tissues are generally required for HLA alloimmunization, the effect of the 
      extent of major histocompatibility complex (MHC) mismatch between donor and 
      recipient is poorly understood. STUDY DESIGN AND METHODS: A novel mouse was 
      generated that allows the expression of a single MHC Class I alloantigen, K(d) . 
      Alloimmune responses to K(d) were studied in C57BL/6 mice transfused with 
      splenocytes from different donor mice, allowing the analysis of responses to K(d) 
      as an isolated alloantigen, or in the context of additional mismatched MHC 
      molecules. Advanced tools were utilized to study responses to K(d) , including 
      T-cell receptor transgenic mice that recognize the immunodominant K(d) peptide 
      presented by C57BL/6 mice to CD4+ T cells. RESULTS: A single MHC Class I 
      alloantigen mismatch is less immunogenic than when the same alloantigen is 
      encountered in the context of additional mismatched MHC alloantigens. This 
      difference is due, at least in part, to induction of CD4+ helper T cells, as the 
      effect is overcome by increasing either mature CD4+ T-cell help through 
      immunization or by increasing the precursor frequency of naive CD4+ T cells by 
      adoptive transfer from T-cell receptor transgenic donors. CONCLUSION: These 
      findings indicate that the immunogenicity of a single alloantigen can be affected 
      by the context in which it is encountered, demonstrating the potential for 
      cooperative effects between different mismatched MHC alloantigens.
CI  - (c) 2019 AABB.
FAU - Hudson, Krystalyn E
AU  - Hudson KE
AD  - BloodworksNW Research Institute, Seattle, Washington.
AD  - Department of Laboratory Medicine, University of Washington School of Medicine, 
      Seattle, Washington.
FAU - Wong, Andrea S L
AU  - Wong ASL
AD  - BloodworksNW Research Institute, Seattle, Washington.
FAU - Richards, Amanda L
AU  - Richards AL
AD  - BloodworksNW Research Institute, Seattle, Washington.
FAU - Kapp, Linda M
AU  - Kapp LM
AD  - BloodworksNW Research Institute, Seattle, Washington.
FAU - Zimring, James C
AU  - Zimring JC
AD  - BloodworksNW Research Institute, Seattle, Washington.
AD  - Department of Laboratory Medicine, University of Washington School of Medicine, 
      Seattle, Washington.
AD  - Department of Medicine, Division of Hematology, University of Washington School 
      of Medicine, Seattle, Washington.
LA  - eng
GR  - R01 HL114525/HL/NHLBI NIH HHS/United States
GR  - R01 HL114525-01A1/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190125
PL  - United States
TA  - Transfusion
JT  - Transfusion
JID - 0417360
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Isoantigens)
RN  - 0 (Receptors, Antigen, T-Cell)
MH  - Animals
MH  - Blood Platelets/*immunology/pathology
MH  - Disease Models, Animal
MH  - Histocompatibility Antigens Class II/genetics/*immunology
MH  - Humans
MH  - Isoantigens/genetics/*immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - *Platelet Transfusion
MH  - Receptors, Antigen, T-Cell/genetics/*immunology
MH  - T-Lymphocytes, Helper-Inducer/*immunology/pathology
MH  - Transfusion Reaction/genetics/pathology
PMC - PMC7025900
MID - NIHMS1000038
COIS- Conflict of interest: The authors have no conflicts of interest to report 
      relevant to the work contained in the submitted manuscript.
EDAT- 2019/01/27 06:00
MHDA- 2019/07/30 06:00
PMCR- 2020/02/17
CRDT- 2019/01/26 06:00
PHST- 2017/12/27 00:00 [received]
PHST- 2018/09/11 00:00 [revised]
PHST- 2018/09/12 00:00 [accepted]
PHST- 2019/01/27 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2019/01/26 06:00 [entrez]
PHST- 2020/02/17 00:00 [pmc-release]
AID - 10.1111/trf.15109 [doi]
PST - ppublish
SO  - Transfusion. 2019 Feb;59(2):744-753. doi: 10.1111/trf.15109. Epub 2019 Jan 25.