Monomeric recombinant MHC molecules useful for manipulation of antigen-specific T-cells

摘要

The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.

主权项

1. An isolated recombinant nucleic acid molecule encoding a major histocompatibility complex-class II (MHC class II) component in the form of a single chain (sc) polypeptide comprising α1 and β1 domains of an HLA-DR protein, wherein the amino terminus of the α1 domain is covalently linked to the carboxy terminus of the β1 domain, wherein the MHC class II component does not include an α2 or β2 domain, and wherein the MHC class II component is modified by substitution of one or more hydrophobic residues with a polar or charged residue, wherein the one or more hydrophobic residues are selected from residues V6, I8, A10, F12, and L14 of the α1 domain.