Abstract
Abstract
Background
Cow antibodies are very unusual in having exceptionally long CDR H3 regions. The genetic basis for this length largely derives from long heavy chain diversity (DH) regions, with a single “ultralong” DH, IGHD8–2, encoding over 50 amino acids. Many bovine IGHD regions have sequence similarity but have several nucleotide repeating units that diversify their lengths. Genomically, most DH regions exist in three clusters that appear to have formed from DNA duplication events. However, the relationship between the genomic arrangement and long CDR lengths is unclear.
Results
The DH cluster containing IGHD8–2 underwent a rearrangement and deletion event in relation to the other clusters in the region corresponding to IGHD8–2, with possible fusion of two DH regions and expansion of short repeats to form the ultralong IGHD8–2 gene.
Conclusions
Length heterogeneity within DH regions is a unique evolutionary genomic mechanism to create immune diversity, including formation of ultralong CDR H3 regions.
Funder
National Institute of General Medical Sciences
National Institute of Child Health and Human Development
Publisher
Springer Science and Business Media LLC
Cited by
7 articles.
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