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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-7-1
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pubmed:abstractText |
Minor histocompatibility (H) antigens crucially affect the outcome of human leukocyte antigen (HLA)-identical allogeneic stem cell transplantation (SCT). To understand the basis of alloimmune responses against minor H antigens, identification of minor H peptides and their antigenicity-determining mechanisms is essential. Here we report the identification of HA-3 and its encoding gene. The HA-3 peptide, VTEPGTAQY (HA-3T), is encoded by the lymphoid blast crisis (Lbc) oncogene. We thus show for the first time that a leukemia-associated oncogene can give rise to immunogenic T-cell epitopes that may have participated in antihost and antileukemic alloimmune responses. Genotypic analysis of HA-3- individuals revealed the allelic counterpart VMEPGTAQY (HA-3M). Despite the lack of T-cell recognition of HA-3- cells, the Thr-->Met substitution had only a modest effect on peptide binding to HLA-A1 and a minimal impact on recognition by T cells when added exogenously to target cells. This substitution did not influence transporter associated with antigen processing (TAP) transport, but, in contrast to the HA-3T peptide, HA-3M is destroyed by proteasome-mediated digestion. Thus, the immunogenicity of minor H antigens can result from proteasome-mediated destruction of the negative allelic peptide.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/A Kinase Anchor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/AKAP13 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A1 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TAP1 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-4971
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pubmed:author |
pubmed-author:BloklandElsE,
pubmed-author:BricknerAnthony GAG,
pubmed-author:CaldwellJennifer AJA,
pubmed-author:EisenlohrLaurence CLC,
pubmed-author:EngelhardVictor HVH,
pubmed-author:GoulmyElsE,
pubmed-author:HuntDonald FDF,
pubmed-author:MollahSahanaS,
pubmed-author:OssendorpFerryF,
pubmed-author:PierceRichard ARA,
pubmed-author:PoolJosJ,
pubmed-author:ShabanowitzJeffreyJ,
pubmed-author:SpieringsEricE,
pubmed-author:TatsisNiaN,
pubmed-author:ZegveldSuzanneS,
pubmed-author:van VeelenPeterP
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
621-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12663445-A Kinase Anchor Proteins,
pubmed-meshheading:12663445-ATP-Binding Cassette Transporters,
pubmed-meshheading:12663445-Acute Disease,
pubmed-meshheading:12663445-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:12663445-Alleles,
pubmed-meshheading:12663445-Amino Acid Sequence,
pubmed-meshheading:12663445-Amino Acid Substitution,
pubmed-meshheading:12663445-Antigen Presentation,
pubmed-meshheading:12663445-CD8-Positive T-Lymphocytes,
pubmed-meshheading:12663445-Clone Cells,
pubmed-meshheading:12663445-Cysteine Endopeptidases,
pubmed-meshheading:12663445-Epitopes, T-Lymphocyte,
pubmed-meshheading:12663445-Female,
pubmed-meshheading:12663445-Genotype,
pubmed-meshheading:12663445-HLA-A1 Antigen,
pubmed-meshheading:12663445-Humans,
pubmed-meshheading:12663445-Leukemia, Myeloid,
pubmed-meshheading:12663445-Male,
pubmed-meshheading:12663445-Molecular Sequence Data,
pubmed-meshheading:12663445-Multienzyme Complexes,
pubmed-meshheading:12663445-Pedigree,
pubmed-meshheading:12663445-Peripheral Blood Stem Cell Transplantation,
pubmed-meshheading:12663445-Polymorphism, Genetic,
pubmed-meshheading:12663445-Proteasome Endopeptidase Complex,
pubmed-meshheading:12663445-Protein Isoforms,
pubmed-meshheading:12663445-Protein Processing, Post-Translational,
pubmed-meshheading:12663445-Proto-Oncogene Proteins,
pubmed-meshheading:12663445-Sequence Alignment,
pubmed-meshheading:12663445-Sequence Homology, Amino Acid
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pubmed:year |
2003
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pubmed:articleTitle |
The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein.
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pubmed:affiliation |
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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