Inhibition of Ii expression in mammalian cells

A method for stimulating an immune response in a mammal, the immune response being directed toward an antigenic epitope of interest on the surface of an MHC Class II molecule-positive cell in which Ii protein expression is suppressed, the method comprising:

• a) providing an MHC Class II molecule-positive cell which expresses an antigenic epitope of interest;
• b) introducing into the cell of step a) an expressible reverse gene construct, comprising a DNA molecule which encodes an RNA molecule which is complementary to an mRNA molecule which encodes human Ii protein, the RNA molecule having the ability to hybridize with the mRNA molecule thereby inhibiting translation of the mRNA molecule;
• and
• c) immunizing the mammal with either the cell of step b) or an MHC Class II molecule complexed with an antigenic epitope of interest derived from the cell of step b).

A method for targeting a type of cell of an individual for an immunological response, the type of cell being characterized by the expression of an identifying antigen, the method comprising:

• a) providing, in culture, peripheral blood mononuclear cells of the individual including antigen presenting cells;
• b) introducing into the antigen presenting cells of the culture of step a), an inhibitor of Ii synthesis;
• and
• c) introducing an expressible nucleic acid sequence encoding the identifying antigen into the cells in the culture under conditions appropriate for expression.

A method for targeting an antigen in an individual for an immunological response, the method comprising:

• a) providing, in culture, peripheral blood mononuclear cells of the individual including naturally occurring antigen presenting cells;
• b) introducing into the antigen presenting cells of the culture of step a), an inhibitor of Ii synthesis;
• and
• c) introducing into the naturally occurring antigen presenting cells of the culture of step a), an expressible nucleic acid sequence encoding the antigen to be targeted for immunological response.

A method for displaying an antigenic epitope of interest on the surface of an MHC Class II molecule-positive cell, in which Ii protein expression is suppressed, the method comprising:

• a) providing a cell which is either MHC Class II molecule-positive cell or is induced to express MHC Class II molecules and which expresses an antigenic epitope of interest;
• b) introducing into the cell of step a) with a recombinant vector comprising an expressible nucleic acid sequence encoding a protein, the expression of which, in an MHC Class II molecule-negative cell, results in the induction of MHC Class II molecules on the surface of the cell;
• and
• c) introducing into the cell of step a) a copolymer of from 10 to 50 nucleotide bases, the copolymer being characterized by the ability to hybridize specifically to a target region of the RNA molecule encoding mammalian Ii protein under physiological conditions thereby inhibiting Ii expression.

A method for stimulating an immune response in a mammal, the immune response being directed toward an antigenic epitope of interest on the surface of an MHC Class II molecule-positive cell, in which Ii protein expression is suppressed, the method comprising:

• a) providing either an MHC Class II molecule-positive cell which expresses an antigenic epitope of interest, or an MHC Class II molecule-negative cell which expresses an antigenic epitope of interest and which is induced to express MHC Class II molecules on its cell surface;
• b) introducing into the cell of step a) a recombinant adenovirus genome comprising an expressible nucleic acid sequence encoding a protein, the expression of which, in an MHC Class II molecule-negative cell, results in the induction of MHC Class II molecules on the surface of the cell;
• c) introducing into the cell of step a) a copolymer of from 10 to 50 nucleotide bases, the copolymer being characterized by the ability to hybridize specifically to a target region of the RNA molecule encoding mammalian Ii protein under physiological conditions thereby inhibiting Ii expression;
• and
• d) introducing into the mammal the cell of step c), or MHC Class II molecules, and bound antigenic epitope of interest derived from the cell of step c).

A method for isolating an antigenic epitope of interest for diagnosis or therapy of a disease process, the method comprising:

• a) providing a culture containing antigen presenting cells;
• b) introducing into the antigen presenting cells, in culture, an expressible nucleic acid sequence encoding a protein, or portion thereof, the protein being specifically associated with a disease process for which diagnosis or therapy is desired;
• and
• c) isolating antigenic epitope peptides from MHC Class II molecules of the antigen presenting cells of step b).

A method for stimulating an immune response in a mammal, the immune response being directed toward a cancer cell-specific antigenic epitope of interest on the surface of a cell in which Ii protein expression is suppressed, the method comprising:

• a) providing an MHC Class II molecule-negative cell which expresses a cancer cell-specific antigenic epitope of interest;
• b) introducing into the cell of step a) a recombinant vector comprising an expressible nucleic acid sequence encoding a protein, the expression of which in an MHC Class II molecule-negative cell results in the induction of MHC Class II molecules on the surface of the cell;
• c) introducing into the cell of step a) an expressible reverse gene construct, comprising a DNA molecule which encodes an RNA molecule which is complementary to an mRNA molecule which encodes human Ii protein, the RNA molecule having the ability to hybridize with the mRNA molecule thereby inhibiting translation of the mRNA molecule;
• and
• d) immunizing the mammal with either the cell of step c) or an MHC Class II molecule complexed with an antigenic epitope of interest derived from the cell of step c).

A method for targeting a type of cell of an individual for an immunological response, the type of cell being characterized by the expression of an identifying antigen, the method comprising:

• a) providing, in culture, peripheral blood mononuclear cells of the individual including antigen presenting cells;
• b) introducing into the antigen presenting cells of the culture of step a), an inhibitor of Ii synthesis;
• c) introducing an expressible nucleic acid sequence encoding the identifying antigen into the cells in the culture under conditions appropriate for expression;
• and
• d) reintroducing the cells of step c) into the individual.

A method for stimulating an immune response in a mammal, the immune response being directed toward a cancer cell-specific antigenic epitope of interest on the surface of a cell in which Ii protein expression is suppressed, the method comprising:

• a) providing an MHC Class II molecule-positive cell which expresses a cancer cell-specific antigenic epitope of interest;
• b) introducing into the cell of step a) an expressible reverse gene construct, comprising a DNA molecule which encodes an RNA molecule which is complementary to an mRNA molecule which encodes human Ii protein, the RNA molecule having the ability to hybridize with the mRNA molecule thereby inhibiting translation of the mRNA molecule;
• and
• c) immunizing the mammal with either the cell of step b) or an MHC Class II molecule complexed with an antigenic epitope of interest derived from the cell of step b).