The Human‐Inducible Costimulator Ligand is Polymorphic

Jacobsen, K.; Ohm‐Laursen, L.; Barington, T.

Inducible costimulator ligand (ICOSL) is a costimulatory molecule related to B7.1 (CD80) and B7.2 (CD86). B cells, monocytes, dendritic cells and endothelial cells express ICOSL. Inducible costimulator (ICOS) interacts with ICOSL, and this interaction leads to signals involved in isotype switching and the development of immunological memory. Hitherto, no polymorphisms of this gene have been described. The aim of this study was to reveal variation of the ICOSL gene in normal individuals. All eight exons, except exon 1, were sequenced with flanking introns in 10 healthy blood donors. Eight single nucleotide polymorphisms (SNPs) and two length polymorphisms were found. One of the SNPs was found in the coding regions of the gene. The base involved was located in exon 3 and caused a conservative amino acid change from valine (GTT) to isoleucine (ATT). Three individuals were heterozygous G/A for the exon polymorphism, while the remaining seven individuals were homozygous for the wildtype G/G. Exon 3 encodes the immunoglobulin variable (IgV)‐like domain of the molecule which is situated outside the cell. This means that the amino acid could be critical for the stability of the molecule or could constitute part of the binding site for ICOS. The results form the basis for further experiments to find possible associations of the alleles to diseases caused by immune dysregulation. Especially, the exon 3 variant is interesting and could play a role for the development of immunological diseases. Besides, it would be interesting to see whether both exon 3 alleles are expressed or only the wildtype allele is functional.