IgM-mediated receptor clustering and cell modulation
View Patent ↗Materials and methods for using multivalent molecules (e.g., antibodies) to modulate cellular function. A molecule can be targeted to a particular type of cell, either through direct binding to an epitope on the surface of the cell, or through a linker that recognizes both the multivalent molecule and a marker on the cell surface.
1. A chimeric polypeptide comprising a first amino acid sequence and a second amino acid sequence, wherein the first amino acid sequence comprises a Kb amino acid sequence, and where the second amino acid sequence comprises an epitope to which a multivalent molecule binds, wherein the multivalent molecule is an IgM antibody hIgM12 and the second amino acid sequence comprises SEQ ID NO: 16 or SEQ ID NO:17.
2. The chimeric polypeptide of claim 1 , wherein the second amino acid sequence comprises SEQ ID NO: 17.
3. A linker molecule for targeting IgM antibody hIgM12 to a cell in the oligodendrocyte lineage, wherein the linker molecule is a polypeptide comprising (i) an amino acid sequence SEQ ID NO: 16 or SEQ ID NO: 17 comprising an epitope to which hIgM12 specifically binds and (ii) an amino acid sequence that binds specifically to an epitope or marker on the surface of the cell in the oligodendrocyte lineage.
4. The linker molecule of claim 3 wherein the cell is an oligodendrocyte.
5. A method for targeting a multivalent molecule to a cell in the oligodendrocyte lineage wherein the multivalent molecule is an IgM antibody hIgM12, comprising:
(a) contacting the cell in the oligodendrocyte lineage with a linker molecule, wherein the linker molecule includes (i) an amino acid sequence comprising an epitope to which the multivalent molecule specifically binds comprising SEQ ID NO: 16 or SEQ ID NO:17 and (ii) an amino acid sequence that binds specifically to a marker on the outer surface of the cell in the oligodendrocyte lineage; and
(b) contacting the cell in the oligodendrocyte lineage with the multivalent molecule.
6. The method of claim 5 , wherein the linker molecule consists of a polypeptide.
7. The method of claim 5 , wherein the linker molecule is a chimeric antibody.
8. A method for targeting a multivalent molecule to a cell in the oligodendrocyte lineage wherein the multivalent molecule is an IgM antibody hIgM12, comprising:
(a) contacting the cell in the oligodendrocyte lineage with a nucleic acid encoding a polypeptide, wherein the polypeptide includes (i) an amino acid sequence that directs the polypeptide to the cell in the oligodendrocyte lineage's plasma membrane and (ii) an amino acid sequence comprising an epitope to which the multivalent molecule specifically binds wherein the sequence comprises SEQ ID NO: 16 or SEQ ID NO:17;
(b) culturing the cell in the oligodendrocyte lineage under conditions in which the polypeptide is expressed and localized to the plasma membrane such that the epitope is located on the exterior of the cell; and
(c) contacting the cell in the oligodendrocyte lineage with the multivalent molecule.