Ligand-dependent selection of the receptor gene: segregation of IL-2 binding activity and anti-Tac reactivity by a single amino acid alteration in the Tac antigen (p55).
The Tac antigen (p55, CD25) is a 55 kDa glycoprotein that binds interleukin 2 at low affinity (Kd congruent to 10-50 nM). Expression of the Tac antigen is induced in the activated human T cells to constitute the functional, high-affinity IL-2 receptors (IL-2Rs) (Kd congruent to 10 pM) in conjunction with p70-75. A monoclonal antibody, anti-Tac, recognizes this molecule and inhibits the binding of IL-2 to both high- and low-affinity IL-2Rs. This observation indicates that IL-2 and anti-Tac binding sites are located close to each other within the Tac molecule. In this report, by utilizing a novel approach, we selected cDNAs encoding the Tac antigen variants whose reactivity with anti-Tac is greatly reduced, while retaining their IL-2 binding activity. Each of the mutant cDNAs contained a point (G----A) mutation resulting in an amino acid substitution at the particular amino-terminal portion of the Tac molecule (Asp-4). These results demonstrate that N-terminal amino acid Asp-4 is involved in the epitope recognized by anti-Tac, and that IL-2 binding site and anti-Tac binding site are structurally separable from each other in the Tac molecule.
Minamoto
S
S
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Itoh
S
S
Kono
T
T
Doi
T
T
Hatakeyama
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D015375:Receptors, Interleukin-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D015375:Receptors, Interleukin-2; D004247:DNA