Molecular analysis of HLA-B35 alleles and their relationship to HLA-B15 alleles.
The HLA-B35 serotype is one of the largest allelic groups of HLA class I molecules and includes four isotypes. Of the four, the B35 variant isoform is relatively rare and is the most acidic form. DNA sequencing of the rare isoforms revealed three alleles, B*1522, B*3511, and B*3517. A phylogenetic tree of HLA-B15- and HLA-B35-related alleles for the exon 2 and 3 nucleotide sequences showed that exon 2 of B*1522 clusters with B35 alleles whereas exon 3 clusters with B15 alleles. Branches of the tree suggest that the serodeterminants of B35, B62, B63, and B70 may reside in the alpha 1 domain, encoded by exon 2. The B*1520 and B*1522 genes, which type as B62 and B35, respectively, are hybrid molecules alternatively using exon 2 and exon 3 sequences of B*3501 and B*1501. A comparison of intron 2 sequences for B*3501, B*1501 and B*1522 suggests that the recombination site may have been in the region at the 3' end of intron 2. Despite being flanked by two highly polymorphic exons (exons 2 and 3), intron 2 is relatively well conserved in the B-locus, and it is characterized by seven to eight tandem repeats of the CGGGG pentanucleotide. A high degree of sequence homology and repetitive sequences are essential for a significant frequency of recombination. In this report, we reveal more about the complex evolutionary history of the HLA-B alleles.
Cereb
N
N
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. n-cereb@ski.mskcc.org
Kim
C
C
Hughes
A L
AL
Yang
S Y
SY
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D019143:Evolution, Molecular; D015235:HLA-B Antigens / Q000235:genetics*; D059910:HLA-B15 Antigen; D015797:HLA-B35 Antigen / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D015235:HLA-B Antigens; D059910:HLA-B15 Antigen; D015797:HLA-B35 Antigen