PMID- 19624613 OWN - NLM STAT- MEDLINE DCOM- 20091222 LR - 20221207 IS - 1399-0039 (Electronic) IS - 0001-2815 (Linking) VI - 74 IP - 4 DP - 2009 Oct TI - 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. PG - 330-5 LID - 10.1111/j.1399-0039.2009.01315.x [doi] AB - 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. FAU - Kelsch, R AU - Kelsch R AD - Institute of Transfusion Medicine and Transplantation Immunology, University Clinics of Muenster, Muenster, Germany. kelsch@uni-muenster.de FAU - Binder, T M C AU - Binder TM FAU - Elsner, H A AU - Elsner HA FAU - Eiermann, T H AU - Eiermann TH FAU - Sibrowski, W AU - Sibrowski W LA - eng PT - Journal Article DEP - 20090715 PL - England TA - Tissue Antigens JT - Tissue antigens JID - 0331072 RN - 0 (Complementarity Determining Regions) RN - 0 (HLA-DQ Antigens) RN - 0 (HLA-DQ3 antigen) RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DR Serological Subtypes) RN - 0 (HLA-DR11 antigen) RN - 0 (HLA-DRB1 Chains) RN - 0 (HLA-DRB1*03:01 antigen) SB - IM MH - Base Sequence MH - Complementarity Determining Regions/*genetics MH - Female MH - HLA-DQ Antigens/*genetics MH - HLA-DR Antigens/*blood/*genetics MH - HLA-DR Serological Subtypes MH - HLA-DRB1 Chains MH - Haplotypes/*genetics MH - Humans MH - Male MH - Molecular Sequence Data MH - Pedigree MH - Phylogeny MH - Sequence Homology, Nucleic Acid MH - White People/*genetics EDAT- 2009/07/25 09:00 MHDA- 2009/12/23 06:00 CRDT- 2009/07/24 09:00 PHST- 2009/07/24 09:00 [entrez] PHST- 2009/07/25 09:00 [pubmed] PHST- 2009/12/23 06:00 [medline] AID - TAN1315 [pii] AID - 10.1111/j.1399-0039.2009.01315.x [doi] PST - ppublish SO - Tissue Antigens. 2009 Oct;74(4):330-5. doi: 10.1111/j.1399-0039.2009.01315.x. Epub 2009 Jul 15.