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.

Détails

ID Serval
serval:BIB_7D539D44D7DB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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.
Périodique
Tissue Antigens
Auteur(s)
Grundschober C., Rufer N., Sanchez-Mazas A., Madrigal A., Jeannet M., Roosnek E., Tiercy J.M.
ISSN
0001-2815
Statut éditorial
Publié
Date de publication
1997
Peer-reviewed
Oui
Volume
49
Numéro
6
Pages
612-623
Langue
anglais
Résumé
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.
Mots-clé
ABO Blood-Group System, Alleles, Amino Acid Sequence, Base Sequence, Bone Marrow Transplantation, DNA, Complementary, Gene Frequency, HLA-C Antigens/genetics, HLA-C Antigens/immunology, HLA-DR Antigens/genetics, Haplotypes, Histocompatibility Testing, Humans, Linkage Disequilibrium, Molecular Sequence Data, T-Lymphocytes, Cytotoxic/immunology
Pubmed
Web of science
Création de la notice
13/10/2009 9:20
Dernière modification de la notice
20/08/2019 15:38
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