An HLA-DR11/DQ3 haplotype with a DRB1*0301 sequence motif in the third hypervariable region of the HLA-DR beta-1 chain: molecular and serological analysis of its generation in a European Caucasian family.
The formation of a new human leukocyte antigen (HLA)-DRB1 allele (DRB1*0340) has been detected during the routine testing of a European Caucasian blood and potential stem cell donor and his family. HLA typing of the donor with two polymerase chain reaction - sequence specific oligonucleotides (PCR-SSO) systems yielded inconclusive results. HLA typing of the family members including sequence-based typing of DRB1 in both directions after haplotype-specific amplification showed that the allele had most likely formed by a double crossover event in exon 2 of the DRB1 gene. The HLA haplotype containing the new allele was most probably derived from the father, who was typed as HLA-DRB1*0301,*1101 and DRB3*0101,*0202. The comparison of the sequences of the paternal DRB1 and DRB3 alleles with the exon 2 sequence of the DRB1*0340 showed that it had most likely formed through an uptake of at least the sequence part codons 58-77 of DRB1*0301 (donor) by DRB1*1101 (acceptor). We suppose that the recombination sites are located in the sequences from codons 38-57 and codons 78-88. At the protein level, more than 50% of the alpha-helical structure of the DRB1*1101 chain is replaced by a DRB1*0301-derived sequence with the exchange of several amino acids. Serological typing of the allele showed HLA-DR3. However, one monoclonal anti-DR11 of five DR11-reactive antibodies reacted positive, which might indicate residual immunogenic epitopes of DRB1*1101. HLA alleles that are most similar to HLA-DRB1*0340 are DRB1*030501, *0317, *0329 and *1107 with at least four amino acid differences in exon 2. In conclusion, HLA-DRB1*0340 is a new allele with unique properties compared with other known HLA-DRB alleles with regard to antigenicity, T-cell receptor-binding and peptide-binding possibilities.
Kelsch
R
R
Institute of Transfusion Medicine and Transplantation Immunology, University Clinics of Muenster, Muenster, Germany. kelsch@uni-muenster.de
Binder
T M C
TM
Elsner
H A
HA
Eiermann
T H
TH
Sibrowski
W
W
D001483:Base Sequence; D022801:Complementarity Determining Regions / Q000235:genetics*; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000097:blood* / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid; D044465:White People / Q000235:genetics*
D022801:Complementarity Determining Regions; D006683:HLA-DQ Antigens; C051569:HLA-DQ3 antigen; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen