SYNTAC POLYPEPTIDES AND USES THEREOF

1 .- 78 . (canceled)

79 . A multimeric polypeptide comprising:

a heterodimeric polypeptide comprising:

a) a first polypeptide comprising, in order from N-terminus to C-terminus:

i) a peptide epitope; and

ii) a first major class II histocompatibility complex (MHC) polypeptide;

b) a second polypeptide comprising a second class II MHC polypeptide, and

c) at least one immunomodulatory polypeptide,

wherein the first and/or the second polypeptide comprises the at least one immunomodulatory polypeptide,

wherein the peptide epitope is an epitope of a self antigen, and

wherein the multimeric polypeptide comprises an immunoglobulin (Ig) Fc polypeptide or a non-Ig scaffold.

80 . The multimeric polypeptide of claim 79 , wherein the multimeric polypeptide comprises:

a1) a first polypeptide comprising, in order from N-terminus to C-terminus:

i) an epitope; and

ii) a first class II MHC polypeptide; and

b1) a second polypeptide comprising, in order from N-terminus to C-terminus:

i) at least one immunomodulatory polypeptide;

iii) a second class II MHC polypeptide; and

ii) an immunoglobulin (Ig) Fc polypeptide; or

a2) a first polypeptide comprising, in order from N-terminus to C-terminus:

i) an epitope;

ii) a first class II MHC polypeptide; and

iii) at least one immunomodulatory polypeptide; and

b2) a second polypeptide comprising, in order from N-terminus to C-terminus:

i) a second class II MHC polypeptide; and

ii) an Ig Fc polypeptide; or

a3) a first polypeptide comprising, in order from N-terminus to C-terminus:

i) an epitope; and

ii) a first class II MHC polypeptide; and

b3) a second polypeptide comprising, in order from N-terminus to C-terminus:

i) a second class II MHC polypeptide; and

ii) an Ig Fc polypeptide; and

iii) at least one immunomodulatory polypeptide.

81 . The multimeric polypeptide of claim 79 , wherein the first class II MHC polypeptide is an MHC Class II beta chain polypeptide; and wherein the second class II MHC polypeptide is an MHC class II alpha chain polypeptide.

82 . The multimeric polypeptide of claim 80 , wherein the first class II MHC polypeptide is an MHC Class II beta chain polypeptide; and wherein the second class II MHC polypeptide is an MHC class II alpha chain polypeptide.

83 . The multimeric polypeptide of claim 79 , wherein the at least one immunomodulatory polypeptide is selected from a 4-1BBL polypeptide, an ICOS-L polypeptide, an OX-40L polypeptide, a CD80 polypeptide, a CD86 polypeptide, a PD-L1 polypeptide, a FasL polypeptide, a cytokine, and a PD-L2 polypeptide.

84 . The multimeric polypeptide of claim 83 , wherein the at least one immunomodulatory polypeptide is selected from a PD-L1 polypeptide, a FasL polypeptide and a cytokine.

85 . The multimeric polypeptide of claim 82 , wherein the at least one immunomodulatory polypeptide is selected from a PD-L1 polypeptide, a FasL polypeptide and a cytokine.

86 . The multimeric polypeptide of claim 79 , comprising 2 or more immunomodulatory polypeptides.

87 . The multimeric polypeptide of claim 86 , wherein the 2 or more immunomodulatory polypeptides are in tandem.

88 . A protein comprising two of the multimeric polypeptides of claim 79 , wherein each of the two multimeric polypeptides comprises an immunoglobulin (Ig) Fc polypeptide.

89 . A nucleic acid comprising a nucleotide sequence encoding a first and/or second polypeptide according to claim 79 .

90 . An expression vector comprising the nucleic acid of claim 89 .

91 . A host cell genetically modified with the expression vector of claim 90 .

92 . A method of selectively inhibiting the activity and/or reducing the number of a self-reactive T cell, the method comprising contacting the T cell in vitro with the multimeric polypeptide of claim 79 , wherein said contacting selectively inhibits the activity and/or reduces the number of the self-reactive T cells.

93 . A method of treating an autoimmune disorder in an individual, the method comprising administering to the individual an effective amount of a multimeric polypeptide of claim 79 .

94 . A pharmaceutical composition comprising the multimeric polypeptide of claim 79 .

95 . A method of selectively activating a target T cell that is specific for the peptide epitope present in the multimeric polypeptide, the method comprising contacting the target T cell with a multimeric polypeptide of claim 79 , wherein the target T cell is an epitope-specific CD4 + T cell.

96 . A multimeric polypeptide of claim 95 , wherein the epitope-specific CD4 + T cell is a CD4 + /CD25 + /FoxP3 + regulatory T cell.

97 . A composition of matter comprising:

at least one heterodimer comprising:

a) a first fusion polypeptide comprising, in order from N-terminus to C-terminus:

i) a cancer-associated T-cell peptide epitope, wherein the peptide has a length of from 8 amino acids to 12 amino acids; and

ii) first class I major histocompatibility complex (MHC) polypeptide;

b) a second fusion polypeptide comprising, in order from N-terminus to C-terminus:

i) at least one activating immunomodulatory polypeptide, wherein the at least one immunomodulatory polypeptide is a cytokine, a 4-1BBL polypeptide, an ICOS-L polypeptide, an OX-40L polypeptide, a CD80 polypeptide, or a CD86 polypeptide;

ii) a second class I MHC polypeptide, and

iii) an immunoglobulin (Ig) Fc polypeptide,

wherein the at least one activating immunomodulating polypeptide causes an increase in the proliferation and/or cytotoxic activity of a target T cell comprising a T cell receptor that binds the epitope.

98 . A multimeric polypeptide comprising:

a heterodimeric polypeptide comprising:

a) a first polypeptide comprising, in order from N-terminus to C-terminus:

i) a peptide epitope; and

ii) a first major histocompatibility complex (MHC) polypeptide;

b) a second polypeptide comprising a second MHC polypeptide, and

c) at least one immunomodulatory polypeptide,

wherein the first and/or the second polypeptide comprises the at least one immunomodulatory polypeptide,

wherein the first MHC polypeptide is a β2-microglobulin polypeptide and wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide,

wherein the peptide epitope is a pathogen-associated epitope, and

wherein the multimeric polypeptide comprises an immunoglobulin (Ig) Fc polypeptide or a non-Ig scaffold.