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
| Autor: | Thomas Eiermann, W. Sibrowski, Thomas M.C. Binder, H. A. Elsner, R. Kelsch |
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| Rok vydání: | 2009 |
| Předmět: |
Male
musculoskeletal diseases Sequence analysis Molecular Sequence Data Immunology Human leukocyte antigen Biology Biochemistry White People Exon immune system diseases HLA-DQ Antigens Sequence Homology Nucleic Acid Genetics Humans Immunology and Allergy Allele skin and connective tissue diseases Phylogeny HLA-DR Serological Subtypes Base Sequence Haplotype HLA-DR Antigens General Medicine Complementarity Determining Regions Molecular biology Pedigree Histocompatibility Haplotypes Female Sequence motif HLA-DRB1 Chains |
| Zdroj: | Tissue Antigens. 74:330-335 |
| ISSN: | 1399-0039 0001-2815 |
| DOI: | 10.1111/j.1399-0039.2009.01315.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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