Linked Life Data

9234483

Source:http://linkedlifedata.com/resource/pubmed/id/9234483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-10-20
pubmed:databankReference
pubmed:abstractText
While the influence of HLA-AB and -DRB1 matching on the outcome of bone marrow transplantation (BMT) with unrelated donors is clear, the evaluation of HLA-C has been hampered by its poor serological definition. Because the low resolution of standard HLA-C typing could explain the significant number of positive cytotoxic T lymphocyte precursor frequency (CTLpf) tests found among HLA-AB-subtype, DRB1/B3/B5-subtype matched patient/donor pairs, we have identified by sequencing the incompatibilities recognized by CD8+ CTL clones obtained from such positive CTLpf tests. In most cases the target molecules were HLA-C antigens that had escaped detection by serology (e.g. Cw*1601, 1502 or 0702). Direct recognition of HLA-C by a CTL clone was demonstrated by lysis of the HLA class I-negative 721.221 cell line transfected with Cw*1601 cDNA. Because of the functional importance of Cw polymorphism, a PCR-SSO oligotyping procedure was set up allowing the resolution of 29 Cw alleles. Oligotyping of a panel of 382 individuals (including 101 patients and their 272 potential unrelated donors, 5 related donors and 4 platelet donors) allowed to determine HLA-C and HLA A-B-Cw-DRB1 allelic frequencies, as well as a number of A-Cw, B-Cw, and DRB1-Cw associations. Two new HLA-Cw alleles (Cw*02023 and Cw*0707) were identified by DNA sequencing of PCR-amplified exon 2-intron 2-exon 3 amplicons. Furthermore, we determined the degree of HLA-C compatibility in 287 matched pairs that could be formed from 73 patients and their 184 potential unrelated donors compatible for HLA-AB by serology and for HLA-DRB1/ B3/B5 by oligotyping. Cw mismatches were identified in 42.1% of these pairs, and AB-subtype oligotyping showed that 30% of these Cw-incompatible pairs were also mismatched for A or B-locus subtype. The degree of HLA-C incompatibility was strongly influenced by the linkage with B alleles and by the ABDR haplotypes. Cw alleles linked with B*4403, B*5101, B18, and B62 haplotypes were frequently mismatched. Apparently high resolution DNA typing for HLA-AB does not result in full matching at locus C. Since HLA-C polymorphism is recognized by alloreactive CTLs, such incompatibilities might be as relevant as AB-subtype mismatches in clinical transplantation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0001-2815
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
612-23
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:9234483-ABO Blood-Group System, pubmed-meshheading:9234483-Alleles, pubmed-meshheading:9234483-Amino Acid Sequence, pubmed-meshheading:9234483-Base Sequence, pubmed-meshheading:9234483-Bone Marrow Transplantation, pubmed-meshheading:9234483-DNA, Complementary, pubmed-meshheading:9234483-Gene Frequency, pubmed-meshheading:9234483-HLA-C Antigens, pubmed-meshheading:9234483-HLA-DR Antigens, pubmed-meshheading:9234483-HLA-DRB1 Chains, pubmed-meshheading:9234483-HLA-DRB3 Chains, pubmed-meshheading:9234483-HLA-DRB5 Chains, pubmed-meshheading:9234483-Haplotypes, pubmed-meshheading:9234483-Histocompatibility Testing, pubmed-meshheading:9234483-Humans, pubmed-meshheading:9234483-Linkage Disequilibrium, pubmed-meshheading:9234483-Molecular Sequence Data, pubmed-meshheading:9234483-T-Lymphocytes, Cytotoxic
pubmed:year
1997
pubmed:articleTitle
Molecular characterization of HLA-C incompatibilities in HLA-ABDR-matched unrelated bone marrow donor-recipient pairs. Sequence of two new Cw alleles (Cw*02023 and Cw*0707) and recognition by cytotoxic T lymphocytes.
pubmed:affiliation
Transplantation Immunology Unit, Hôpitaux Universitaires de Genève, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't