Hotspot variation at the CH2-CH3 interface of leporid IgG antibodies (Oryctolagus, Sylvilagus and Lepus).

The European rabbit (Oryctolagus cuniculus) is the only species known to express only one subclass of gamma class immunoglobulin (IgG) antibodies. The rabbit IGHGCH2 (second domain of the gene region encoding the IgG heavy chain constant region) or e locus presents two serologically defined alleles, the e14 and e15 allotypes. These are correlated with amino acid variation at position 309, which is located within the target region of the neonatal FcRn receptor. The e14 and e15 markers were also observed in other lagomorph species. Population genetic research has indicated that polymorphism at this locus is sustained by selection. We present here the IGHGCH2 exon sequences for 12 species of rabbit and hare (genera Oryctolagus, Sylvilagus and Lepus). The inferred amino acid sequences reveal that, despite an overall sequence identity of 97%, five different residues can occur at position 309. As for Oryctolagus, the e15 allotype was always associated with the presence of an Ala309 codon. In all but one case, this codon defined an allotype-specific ThaI restriction site. The potential of PCR/ThaI restriction fragment length polymorphism (RFLP) analyses for studying IGHGCH2 variation within and between populations is emphasized.