Family of immunoregulators designated leukocyte immunoglobulin-like receptors (LIR)
AssigneeImmunex Corporation
InventorDavid J. Cosman
Life of this patent
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Abstract
A new family of immunoreceptor molecules of the immunoglobulin superfamily, (LIR) polypeptides is described. Disclosed are sequences encoding LIR family members and their deduced amino acid sequences, polypeptides encoded by DNA that hybridize to oligonucleotide probes having defined sequences, processes for producing polypeptides of the LIR family, and antagonistic antibodies to LIR family members. LIR family members can be used to treat autoimmune diseases and disease states associated with suppressed immune function.
Claims20
An isolated DNA encoding an LIR polypeptide, wherein said LIR polypeptide comprises amino acid sequences selected from the group consisting of:
- a) amino acids 5 to 50 of SEQ ID NO:2;
- and
- b) an amino acid sequence that is at least 77% identical to the sequence of a).
DNA encoding an LIR polypeptide, wherein said LIR polypeptide comprises the amino acid sequence:
- Leu Xaaa Leu Ser Xaab Xaac Pro Arg Thr Xaad Xaae Gln Xaaf Gly Xaag Xaah Pro Xaai Pro Thr Leu Trp Ala Glu Pro Xaaj Ser Phe Ile Xaaj Xaa70 Ser Asp Pro Lys Leu Xaah Leu Val Xaam Thr Gly
- where Xaaa is Gly or Arg;
- Xaab is Leu or Val;
- Xaac is Gly or Asp;
- Xaad is His Arg or Cys;
- Xaae is Val or Met;
- Xaaf is Ala or Thr;
- Xaag is His Pro or Thr;
- Xaah Leu Ile or Phe;
- Xaai is Gly Asp or Ala;
- Xaaj is Thr Ile Ser or Ala;
- Xaak is Gly or Val;
- Xaam is Met or Ala;
- and Xaa70 is a sequence of 70 amino acids.
DNA encoding an LIR polypeptide, wherein said LIR polypeptide is encoded by DNA selected from the group consisting of:
- a) DNA capable of hybridizing under highly stringent conditions to a probe consisting essentially of nucleotides 310 to 1684 of SEQ ID NO:1;
- and
- b) DNA capable of hybridizing under highly stringent conditions to DNA complementary to the probe of a),
- wherein the highly stringent conditions comprise a hybridizing temperature of at least 63° C.
An isolated DNA encoding an LIR polypeptide, wherein said LIR polypeptide comprises an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of:
- a) SEQ ID NO:2;
- b) SEQ ID NO:4;
- c) SEQ ID NO:8;
- d) SEQ ID NO:10;
- e) SEQ ID NO:12;
- f) SEQ ID NO:14;
- g) SEQ ID NO:16;
- h) SEQ ID NO:18;
- i) SEQ ID NO:20;
- and
- j) SEQ ID NO:22.
An isolated DNA encoding a soluble LIR polypeptide, wherein said soluble LIR polypeptide comprises an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of:
- a) the extracellular domain of LIR family members comprising sequences selected from the group consisting of:
- amino acids x1 to 458 of SEQ ID NO:2, wherein x1 is amino acid 1 or 17;
- amino acids x2 to 459 of SEQ ID NO:4, wherein x2 is amino acid 1 or 17;
- amino acids x3 to 439 of SEQ ID NO:8, wherein x3 is amino acid 1 or 17;
- amino acids x4 to 458 of SEQ ID NO:10, wherein x4 is amino acid 1 or 17;
- amino acids x5 to 241 of SEQ ID NO:12, wherein x5 is amino acid 1 or 17;
- amino acids x6 to 461 of SEQ ID NO:14, wherein x6 is amino acid 1 or 17;
- amino acids x7 to 449 of SEQ ID NO:16, wherein x7 is amino acid 1 or 17;
- amino acids x8 to 259 of SEQ ID NO:18, wherein x8 is amino acid 1 or 17;
- amino acids x9 to 443 of SEQ ID NO:20, wherein x9 is amino acid 1 or 17;
- and,
- amino acids x10 to 456 of SEQ ID NO:22, wherein x10 is amino acid 1 or 17;
- b) a fragment of any of the LIR extracellular domains of a), wherein said soluble LIR polypeptide binds an MHC molecule.
An LIR polypeptide comprising an amino acid sequence selected from the group consisting of:
- a) amino acids 5 to 50 of SEQ ID NO:2;
- and
- b) an amino acid sequence that is at least 77% identical to the sequence of a).
An LIR polypeptide comprising the amino acid sequence:
- Leu Xaaa Leu Ser Xaab Xaac Pro Arg Thr Xaad Xaae Gln Xaaf Gly Xaag Xaah Pro Xaai Pro Thr Leu Trp Ala Glu Pro Xaaj Ser Phe Ile Xaaj Xaa70 Ser Asp Pro Lys Leu Xaak Leu Val Xaam Thr Gly
- where Xaaa is Gly or Arg;
- Xaab is Leu or Val;
- Xaac is Gly or Asp;
- Xaad is His Arg or Cys;
- Xaae is Val or Met;
- Xaaf is Ala or Thr;
- Xaag is His Pro or Thr;
- Xaah Leu Ile or Phe;
- Xaai is Gly Asp or Ala;
- Xaaj is Thr Ile Ser or Ala;
- Xaak is Gly or Val;
- Xaam is Met or Ala;
- and Xaa70 is a sequence of 70 amino acids.
An isolated polypeptide encoded by DNA selected from the group consisting of:
- a) DNA capable of hybridizing under highly stringent conditions to a probe consisting essentially of nucleotides 310 to 1684 of SEQ ID NO:1;
- and
- b) DNA capable of hybridizing under highly stringent conditions to DNA complementary to the probe of a),
- wherein the highly stringent conditions comprise a hybridizing temperature of at least 63° C.
A soluble LIR polypeptide comprising an amino acid sequence that is at least 90% identical to a sequence selected from the group consisting of:
- a) the extracellular domain of LIR family members, the extracellular domains selected from the group consisting of
- amino acids x1 to 458 of SEQ ID NO:2, wherein x1 is amino acid 1 or 17;
- amino acids x2 to 459 of SEQ ID NO:4, wherein x2 is amino acid 1 or 17;
- amino acids x3 to 439 of SEQ ID NO:8, wherein x3 is amino acid 1 or 17;
- amino acids x4 to 458 of SEQ ID NO:10, wherein x4 is amino acid 1 or 17;
- amino acids x5 to 241 of SEQ ID NO:12, wherein x5 is amino acid 1 or 17;
- amino acids x6 to 461 of SEQ ID NO:14, wherein x6 is amino acid 1 or 17;
- amino acids x7 to 449 of SEQ ID NO:16, wherein x7 is amino acid 1 or 17;
- amino acids x8 to 259 of SEQ ID NO:18, wherein x8 is amino acid 1 or 17;
- amino acids x9 to 443 of SEQ ID NO:20, wherein x9 is amino acid 1 or 17;
- and,
- amino acids x10 to 456 of SEQ ID NO:22, wherein x10 is amino acid 1 or 17;
- b) a fragment of any of the LIR extracellular domains of a), wherein the fragment is capable of binding a ligand.
An isolated polypeptide encoded by a DNA selected from the group consisting of:
- a) DNA capable of hybridizing under highly stringent conditions to DNA selected from the group consisting of SEQ ID NO:5 and SEQ ID NO:6, the highly stringent conditions including a hybridizing temperature of at least 68° C.
A fusion protein comprising amino acids 17 to 458 of SEQ ID NO:2 and the Fc region of Ig.
A fusion DNA construct comprising DNA encoding amino acids 17 to 458 of SEQ ID NO:2 and DNA encoding the Fc region of Ig.
Dependencies are inferred from the claim text.