PMID- 12663445
OWN - NLM
STAT- MEDLINE
DCOM- 20030912
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 102
IP  - 2
DP  - 2003 Jul 15
TI  - The minor histocompatibility antigen HA-3 arises from differential 
      proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein.
PG  - 621-9
AB  - 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.
FAU - Spierings, Eric
AU  - Spierings E
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, Leiden, The Netherlands.
FAU - Brickner, Anthony G
AU  - Brickner AG
FAU - Caldwell, Jennifer A
AU  - Caldwell JA
FAU - Zegveld, Suzanne
AU  - Zegveld S
FAU - Tatsis, Nia
AU  - Tatsis N
FAU - Blokland, Els
AU  - Blokland E
FAU - Pool, Jos
AU  - Pool J
FAU - Pierce, Richard A
AU  - Pierce RA
FAU - Mollah, Sahana
AU  - Mollah S
FAU - Shabanowitz, Jeffrey
AU  - Shabanowitz J
FAU - Eisenlohr, Laurence C
AU  - Eisenlohr LC
FAU - van Veelen, Peter
AU  - van Veelen P
FAU - Ossendorp, Ferry
AU  - Ossendorp F
FAU - Hunt, Donald F
AU  - Hunt DF
FAU - Goulmy, Els
AU  - Goulmy E
FAU - Engelhard, Victor H
AU  - Engelhard VH
LA  - eng
GR  - AI 33993/AI/NIAID NIH HHS/United States
GR  - AI20963/AI/NIAID NIH HHS/United States
GR  - AI44134/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030327
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (A Kinase Anchor Proteins)
RN  - 0 (AKAP13 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Protein Isoforms)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (TAP1 protein, human)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - A Kinase Anchor Proteins
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Acute Disease
MH  - Adaptor Proteins, Signal Transducing
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Antigen Presentation
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Clone Cells/immunology
MH  - Cysteine Endopeptidases/*metabolism
MH  - Epitopes, T-Lymphocyte/*genetics/immunology/metabolism
MH  - Female
MH  - Genotype
MH  - HLA-A1 Antigen/metabolism
MH  - Humans
MH  - Leukemia, Myeloid/immunology/therapy
MH  - Male
MH  - Minor Histocompatibility Antigens
MH  - Molecular Sequence Data
MH  - Multienzyme Complexes/*metabolism
MH  - Pedigree
MH  - Peripheral Blood Stem Cell Transplantation
MH  - Polymorphism, Genetic
MH  - Proteasome Endopeptidase Complex
MH  - Protein Isoforms/genetics/metabolism
MH  - *Protein Processing, Post-Translational
MH  - Proto-Oncogene Proteins/*genetics/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
EDAT- 2003/03/29 05:00
MHDA- 2003/09/13 05:00
CRDT- 2003/03/29 05:00
PHST- 2003/03/29 05:00 [pubmed]
PHST- 2003/09/13 05:00 [medline]
PHST- 2003/03/29 05:00 [entrez]
AID - S0006-4971(20)44383-6 [pii]
AID - 10.1182/blood-2003-01-0260 [doi]
PST - ppublish
SO  - Blood. 2003 Jul 15;102(2):621-9. doi: 10.1182/blood-2003-01-0260. Epub 2003 Mar 
      27.