RESUMEN
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.
Asunto(s)
Regiones Determinantes de Complementariedad/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/sangre , Antígenos HLA-DR/genética , Haplotipos/genética , Población Blanca/genética , Secuencia de Bases , Femenino , Subtipos Serológicos HLA-DR , Cadenas HLA-DRB1 , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Filogenia , Homología de Secuencia de Ácido NucleicoAsunto(s)
Trasplante de Médula Ósea/efectos adversos , Cromosomas Humanos X , Enfermedad Granulomatosa Crónica/genética , Enfermedad Granulomatosa Crónica/cirugía , Hemólisis , Transfusión de Linfocitos , Preescolar , Dineínas/genética , Exones , Humanos , Masculino , Glicoproteínas de Membrana/genética , NADPH Oxidasa 2 , NADPH Oxidasas/genética , Eliminación de SecuenciaAsunto(s)
Leucemia/genética , Complicaciones Neoplásicas del Embarazo/genética , Trasplante de Células Madre/métodos , Adolescente , Adulto , Niño , Preescolar , Quimerismo , Femenino , Feto , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Donantes de Tejidos , Adulto JovenRESUMEN
The new HLA-A*9237 differs from HLA-A*020601 by one nonsynonymous nucleotide exchange at codon 127 (AAA to AAC).