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Functional Differences Among Multiple Isoforms of Guinea Pig Decay-Accelerating Factor¹

Guixian Wang^*,, Mayumi Nonaka, Changqing He, Noriko Okada, Izumi Nakashima^* and Hidechika Okada^2,

^* Department of Immunology, Nagoya University School of Medicine, Nagoya, Japan; and Department of Molecular Biology, Nagoya City University School of Medicine, Nagoya, Japan

Decay-accelerating factor (DAF, CD55) is a membrane inhibitor that protects host cells from the autologous C-mediated attack. The guinea pig homologue of DAF consists of multiple isoforms generated by alternative splicing from a single copy gene. These isoforms are mainly comprised of a glycosylphosphatidylinositol (GPI)-anchored form and a transmembrane form (TM) that is not present in human DAF. Both forms occur in at least three variations that differ in the length of the Ser/Thr-rich region (termed ST-a, ST-ab, and ST-abc). We have transfected cDNAs of the six major isoforms into Chinese hamster ovary cells, and their functional differences were evaluated in inhibition of C-mediated cytolysis and C3 deposition, using the transfectants expressing DAF at the same level on cell membranes. The degree of inhibition in both the classical and alternative pathways differed according to the length of the ST region in the order of abc > ab > a in both GPI and TM forms. When GPI and TM forms were compared, those with the ab or abc variation exhibited almost the same activity, whereas a-TM was less efficient than a-GPI. Although several isoforms are expressed constitutively in most of tissues, spermatozoa preferentially express the abc-GPI isoform, suggesting that this isoform offers effective protection to spermatozoa in the female genital tract.

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