Polymorphism of HLA-DR β Chains in DR4, -7, and -9 Haplotypes: Implications for the Mechanisms of Allelic Variation

We have isolated and sequenced cDNA clones corresponding to the DRβ 1 and DRβ 2 loci from two homozygous B-cell lines typed as DR7 (Burkhart) and DR9 (ISK). These nucleotide sequences were compared to β 1 and β 2 chains of other DR haplotypes. The first-domain sequences of β 2 chains are identical i...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1986-12, Vol.83 (23), p.9149-9153
Main Authors: Gregersen, Peter K., Moriuchi, Tetsuya, Karr, Robert W., Obata, Fumiya, Moriuchi, Junko, Maccari, Joan, Goldberg, Donna, Winchester, Robert J., Silver, Jack
Format: Article
Language:English
Subjects:
Alleles
Base Sequence
Biological and medical sciences
Cell lines
Complementary DNA
Evolution
Family members
Fundamental and applied biological sciences. Psychology
Genes. Genome
Genetic loci
Haplotypes
HLA-D Antigens - genetics
HLA-DR Antigens - genetics
Humans
Molecular and cellular biology
Molecular genetics
Molecules
Nucleotides
Polymorphism, Genetic
Three prime untranslated regions
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Summary:We have isolated and sequenced cDNA clones corresponding to the DRβ 1 and DRβ 2 loci from two homozygous B-cell lines typed as DR7 (Burkhart) and DR9 (ISK). These nucleotide sequences were compared to β 1 and β 2 chains of other DR haplotypes. The first-domain sequences of β 2 chains are identical in DR4 and DR7 haplotypes. In addition, there is strong sequence homology within the 3′ untranslated regions of β 1 genes from DR4, -7, and -9 haplotypes, thus confirming the close evolutionary relationship among these three haplotypes. In contrast, the first-domain sequences of β 1 molecules from these haplotypes are very different from each other and do not reflect the DR4, -7, -9 family relationship. Two explanations for the differences in degree of diversity between β 1 and β 2 chains are suggested. The differences may be a consequence of selection pressures; this implies functional differences for products of the β 1 and β 2 loci. Alternatively, closely linked segments of the human class II region may differ in their underlying rates of variation, independent of selection pressures, and this may in part account for the extraordinary diversity found in the β 1 first domain.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.83.23.9149