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Apparent HLA DR triplet due to the coexpression of a DRB5-encoded molecule on a DR1 haplotype
L Gebuhrer1, J M Tiercy, A C Freidel
1Histocompatibility Laboratory, Blood Transfusion Center, Lyon, France.
Insights
Rare human leukocyte antigen (HLA) DR1 cells were found to express a second DR antigen, reacting with anti-DR2 sera. DNA analysis revealed these cells carried both DRB1*0101 and DRB5*0101 alleles, indicating unusual DR1+2* haplotypes.
Area of Science:
- Immunogenetics
- Molecular Biology
- Human Leukocyte Antigen (HLA) system
Background:
- Human Leukocyte Antigen (HLA) DR1 molecules are typically encoded by a single polymorphic DRB1 gene.
- Unusual serological findings revealed rare DR1 cells that also reacted with anti-DR2 sera in certain individuals and families.
- These cells presented as triplets, with normal expression of other DR antigens, posing a diagnostic challenge.
Purpose of the Study:
- To investigate the genetic basis of rare DR1 cells exhibiting cross-reactivity with anti-DR2 sera.
- To characterize the molecular mechanisms underlying these unusual DR1+2* haplotypes.
- To clarify the genetic composition of these atypical HLA haplotypes.
Main Methods:
- Serological typing using anti-DR sera.
- High-resolution typing by DNA oligotyping.
- Sequencing of the DRB first-domain exon.
Main Results:
- Rare DR1 cells cross-reacting with anti-DR2 sera were identified.
- These cells were not typed by standard Human Tissue Cell (HTC) typing for Dw2, Dw12, and Dw21.
- Molecular analysis confirmed the presence of both DRB1*0101 and DRB5*0101 alleles in these DR1 haplotypes.
Conclusions:
- The observed unusual DR1+2* haplotypes are attributed to the co-inheritance of DRB1*0101 and DRB5*0101 alleles.
- This finding expands the understanding of HLA DR polymorphism and potential serological discrepancies.
- Molecular techniques are crucial for accurate characterization of complex HLA haplotypes.
Abstract:
HLA DR1 molecules are coded by a single polymorphic DRB1 gene. We have observed rare DR1 cells in one Caucasoid family and three unrelated individuals that also reacted with some anti-DR2 sera. Since the second DR antigen was normally expressed, these cells appeared as triplets. Contrary to serology, the cells were not typed by HTCs defining Dw2, Dw12, and Dw21. Further investigations on these unusual DR1+2* haplotypes were conducted by DNA oligotyping and by sequencing of the DRB first-domain exon. The results showed that these DR1 haplotypes, besides their DRB1*0101 allele, carried also a DRB5*0101 allele.