Extended HLA-DPB1 polymorphism: an RNA approach for HLA-DPB1 typing

Area of Science:

• Immunogenetics
• Molecular Biology
• Human Leukocyte Antigen (HLA) research

Background:

• Human leukocyte antigen (HLA)-DPB1 alleles are primarily defined by polymorphisms within six hypervariable regions (HVRs) in exon 2.
• The extent of DPB1 polymorphism across its entire coding region remains incompletely characterized.

Purpose of the Study:

• To investigate the representation of DPB1 polymorphism throughout the entire coding region, including untranslated regions (UTRs).
• To develop and apply an RNA sequencing-based typing (SBT) approach for comprehensive DPB1 polymorphism identification.

Main Methods:

• Development of an RNA sequencing-based typing (SBT) method to analyze HLA-DPB1 polymorphism from the 5' UTR to the 3' UTR.
• Study of B-cell lymphoblastoid cell lines expressing 16 distinct DPB1 alleles.

Main Results:

• Discovery of additional HLA-DPB1 polymorphism in exons 1, 3, 4, 5, and both the 5' and 3' UTRs.
• Identification of four novel HLA-DPB1 alleles: DPB1*0502, DPB1*0602, DPB1*0802, and DPB1*0902.
• These new alleles share exon 2 sequences with known alleles but exhibit differences in the extended polymorphic regions, defining two main lineages.

Conclusions:

• The genetic diversity of HLA-DPB1 extends beyond the traditionally studied exon 2 hypervariable regions.
• The identified novel alleles and extended polymorphism contribute to a refined understanding of DPB1 allelic lineages.
• Only HVR F within exon 2 shows correlation with the two major polymorphic lineages identified in the extended DPB1 regions.