Altered peptide ligands
OwnerCharles A. Nicoletteinventor
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Abstract
The present invention provides compositions comprising altered peptide ligands that elicit immune responses in a subject to a native peptide. This invention also provides methods to raise T cell populations as well as a substantially purified population of said T cells. Altered peptide ligands find application in a wide variety of immunomodulatory protocols, including methods to induce or increase an immune response, as well as in methods to suppress or reduce an undesirable immune response, to a corresponding natural epitope.
Claims29
A method to select altered peptide species for administration to a subject, said subject presenting a native ligand for which activation of an immune response against said native ligand is desired, comprising the steps of:
- a. identifying a plurality of altered peptide species capable of eliciting an immune response to said native ligand;
- b. selecting at least two altered peptide species wherein each altered peptide activates a population of T cells having a distinct T cell receptor Vβ recombination.
A method to select altered peptide species for administration to a member of a population of subjects having a given HLA-type, said population presenting a native ligand for which activation of an immune response against said native ligand is desired, comprising the steps of:
- a. identifying a plurality of altered peptide species capable of eliciting an immune response to said native ligand;
- and
- b. selecting two or more of said altered peptide species, wherein each of said altered peptide species activates a T cell having a distinct T cell receptor Vβ recombination in a sample representative of said population.
A composition comprising multiple peptide ligand species directed at a single native ligand, wherein at least two altered peptide species activate a different T cell clone from each other and the T cell receptor Vβ recombination of each of said activated T cell clones is different.
A composition comprising two or more altered peptide species, wherein each of said two or more species is characterized by an ability to activate a different subpopulation of cytotoxic T lymphocytes (CTLs) against the same native ligand.
A kit comprising:
- a. multiple peptide species directed at a single native ligand, wherein
- i. a first peptide species activates a first T cell,
- ii. a second peptide species activates a second T cell, and the T cell receptor Vβ recombination of said first T cell is different from the T cell receptor Vβ recombination of said second T cell;
- and
- b. instructions for the co-administration of each of said peptides.
A method comprising the steps of:
- a. identifying a plurality of altered peptide species characterized by an ability to elicit an immune response against the same native ligand;
- b. determining the T cell receptor Vβ recombination profile of the T cell population activated by each of said identified altered peptide species in a plurality of test subjects;
- and
- selecting at least two or more altered peptide species wherein each of said altered peptide species activates T cell populations having distinct T cell receptor Vβ recombinations in a majority of said test subjects.
Dependencies are inferred from the claim text.