Tac antigen forms disulfide-linked homodimers.
Interleukin 2 (IL-2) is responsible for stimulating T-cell proliferation via interaction with specific, high-affinity membrane receptors. Although an IL-2-binding protein has been identified by virtue of its reactivity with a monoclonal antibody that competes with IL-2 for binding (anti-Tac), the complete and precise structure of functional IL-2 receptors is still unknown. To define further the composition of IL-2 receptors, both IL-2 itself and anti-Tac were used as ligands to adsorb membrane proteins for analysis by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (NaDodSO4/PAGE). A variety of experimental approaches yield results indicating that the Tac antigen, which migrates as a single protein on NaDod-SO4/PAGE under reducing conditions, is also expressed as disulfide-linked homodimers and oligomers. Examined under nonreducing conditions, both activated normal human T cells and cell lines from patients with adult T cell leukemia (HUT-102; MT-1) express Tac antigen homodimers (Mr 105,000) in addition to monomers (Mr 54,000). Formation of the disulfide bond is not a consequence of the experimental procedures used to isolate the proteins for analysis, inasmuch as identical results are obtained when the receptor proteins are iodinated and extracted in the presence of N-ethylmaleimide or prepared for electrophoresis in the absence of heat denaturation. Accordingly, these findings point to Tac antigen associating with itself preferentially. The physiologic significance of homodimer and oligomer formation, especially as it relates to the formation of high-affinity IL-2 receptors, is presently unknown.
Kato
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Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756.
Smith
K A
KA
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D002460:Cell Line; D004220:Disulfides / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005033:Ethylmaleimide; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D046911:Macromolecular Substances; D008970:Molecular Weight; D010449:Peptide Mapping; D011971:Receptors, Immunologic / Q000032:analysis* / Q000276:immunology; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D004220:Disulfides; D007376:Interleukin-2; D046911:Macromolecular Substances; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D005033:Ethylmaleimide