Human fusion proteins between interleukin 2 and IgM heavy chain are cytotoxic for cells expressing the interleukin 2 receptor.
We have constructed a hybrid cDNA coding for a fusion protein between human interleukin 2 and a truncated heavy chain from human immunoglobulin M. The protein encoded by this cDNA contains the entire interleukin 2 sequence including its signal peptide, fused at its C terminus to domains 2 to 4 of the immunoglobulin heavy-chain constant region. Cells transfected with the hybrid cDNA secrete multimeric forms of the fusion protein, which bind specifically to cells bearing high-affinity interleukin 2 receptors. This binding leads either to T-cell proliferation or, if complement is added, to T-cell death. Multimeric forms of the fusion protein with a molecular mass above 500 kDa mediate complement-dependent lysis but trigger proliferation inefficiently when compared with forms with a low molecular mass (< 500 kDa). In contrast, the latter efficiently mediate T-cell proliferation without inducing complement-dependent lysis. The high molecular mass fusion proteins could thus constitute valuable tools for specific immunosuppression in humans.
Vié
H
H
Institut National de la Santé et de la Recherche Médicale (U.211), Unité de Recherche sur les Effecteurs Lymphocytaires, Nantes, France.
Gauthier
T
T
Breathnach
R
R
Bonneville
M
M
Godard
A
A
Dietrich
J
J
Karam
G
G
Gesnel
M C
MC
Peyrat
M A
MA
Jacques
Y
Y
Soulillou
J P
JP
D001483:Base Sequence; D002455:Cell Division; D003165:Complement System Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000235:genetics; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000737:chemistry* / Q000235:genetics; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000737:chemistry* / Q000235:genetics; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D007148:Immunoglobulin mu-Chains; D007376:Interleukin-2; D009838:Oligodeoxyribonucleotides; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D003165:Complement System Proteins; D004247:DNA