Linked Life Data

14564482

Source:http://linkedlifedata.com/resource/pubmed/id/14564482

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-11-17
pubmed:databankReference
pubmed:abstractText
Chronic myelogenous leukemia (CML) is characterized by a t(9;22) translocation resulting in expression of BCR-ABL fusion oncoproteins which are unique to the leukemic cells, necessary for oncogenesis, and potentially immunogenic. We have previously shown that human dendritic cells transduced with an adeno-associated virus vector encoding the fusion region of the b3a2 splice variant (p210(b3a2)) of the BCR-ABL oncoprotein elicit specific T-cell responses in vitro. Two cytotoxic T lymphocyte (CTL) clones generated in this fashion displayed restriction with previously unreported HLA alleles. The first, T1/B9, was CD4(+) and restricted by DRB5*0101 (autologous) or DRB1*1101 (allogeneic). The minimum cytotoxic epitope (MCE) binding to DRB5*0101 for this clone was identified as FKQSSKALQ, overlapping the p210(b3a2) fusion point (boldface). The MCE of DRB1*1101 for this clone differed from DRB5*0101, but also included the fusion point. The clonality of CTL T1/B9 was verified by analyses of TCRalpha/beta chain usage and DNA sequence analyses. To our knowledge, this is the first description of a single clone recognizing both DRB5*0101 and DRB1*1101. The other CTL clone, T1/33, was CD8+ and recognized HLA-B*3501 or B*3503 complexed with an MCE, RPVASDFEP, derived from the c-abl sequence in proximity to the p210(b3a2) fusion point. K562 cells transfected with plasmids encoding HLA-DRA + B5*0101, B*3501, or B*3503 but not controls expressing DRA + DRB1*1501 were lysed by cognate CTL clones, confirming that DRB5*0101 and B*3501/3 could present p210(b3a2) joining region epitopes via endogenous processing. The identification of three additional HLA alleles (DRB5*0101, B*3501, and B*3503) presenting the p210(b3a2) fusion-region antigen will broaden the application of vaccine strategies for targeting CML cells. The findings of single CTL clones cross-recognizing autologous (DRB5*0101 or B*3501) and allogeneic (DRB1*1101 or B*3503) HLA alleles presenting BCR-ABL fusion-region epitopes implies the potential separation of graft-versus-leukemia from graft-versus-host effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0340-7004
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
761-70
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:14564482-Adenoviridae, pubmed-meshheading:14564482-Amino Acid Sequence, pubmed-meshheading:14564482-Antigen Presentation, pubmed-meshheading:14564482-Base Sequence, pubmed-meshheading:14564482-Cytotoxicity, Immunologic, pubmed-meshheading:14564482-Dendritic Cells, pubmed-meshheading:14564482-Fusion Proteins, bcr-abl, pubmed-meshheading:14564482-Genetic Vectors, pubmed-meshheading:14564482-HLA-DR Antigens, pubmed-meshheading:14564482-HLA-DRB1 Chains, pubmed-meshheading:14564482-HLA-DRB5 Chains, pubmed-meshheading:14564482-Humans, pubmed-meshheading:14564482-K562 Cells, pubmed-meshheading:14564482-Molecular Sequence Data, pubmed-meshheading:14564482-Peptide Fragments, pubmed-meshheading:14564482-Receptors, Antigen, T-Cell, alpha-beta, pubmed-meshheading:14564482-T-Lymphocytes, Cytotoxic, pubmed-meshheading:14564482-Transduction, Genetic
pubmed:year
2003
pubmed:articleTitle
Identification of new MHC-restriction elements for presentation of the p210(BCR-ABL) fusion region to human cytotoxic T lymphocytes.
pubmed:affiliation
Division of Hematology and Stem Cell Transplantation, City of Hope National Medical Center and Beckman Research Institute, Duarte, CA 91010, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.