Identification and distribution of three serologically undetected alleles of HLA-DR by oligonucleotide x DNA typing analysis
Recent progress in the molecular biology of human major histocompatibility complex class II genes (HLA-DP, -DQ, -DR) have shown that the genetic complexity and allelic polymorphism are greater than expected. In the case of HLA-DR, three DR ..beta..-chain loci have been identified and linked, two of which (DR ..beta..I and DR ..beta..III, now assigned names HLA-DR1B and HLA-DR3B) are functional. The authors have shown that the HLA micropolymorphism detected at the DNA sequence level can easily be analyzed by hybridization with allele-specific oligonucleotides (HLA oligotyping). In the case of the HLA DRw52 supertypic specificity, which includes the DR3, DR5, DRw6, and DRw8 haplotypes, three alleles, referred to as DRw52a, DRw52b, and DRw52c, have recently been identified at the HLA-DR3B locus by DNA sequencing. Hybridization with locus- and allele-specific oligonucleotide probes (designated 52a, 52b, and 52c) has been performed on DNA from normal individuals forming a panel of 82 haplotypes to establish the distribution of these three alleles. Individuals of the DR3 haplotype had either the DRw52a or DRw52b allele, and individuals of extended haplotype HLA-A1,B8,DR3 had only the DRw52a allele. DR5 individuals all had the DRw52b allele, while individuals of DRw6 haplotype had the DRw52a, -52b, or -52c allele. None of these three alleles are found in DRw8 individuals. Analysis of this micropolymorphism, undetectable by common typing procedures, is therefore now operational for more accurate HLA matching for transplantation and for improving correlations between HLA and disease susceptibility.
- Research Organization:
- Univ. of Geneva Medical School (Switzerland)
- OSTI ID:
- 6271645
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 85:1
- Country of Publication:
- United States
- Language:
- English
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DNA
AUTORADIOGRAPHY
TRANSPLANTS
IMMUNOLOGY
ANTIGENS
ELECTROPHORESIS
GENES
HYBRIDIZATION
LYMPHOCYTES
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PHOSPHORUS 32
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
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ODD-ODD NUCLEI
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PHOSPHORUS ISOTOPES
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550201* - Biochemistry- Tracer Techniques