Compositions for and methods of identifying antigens
AssigneePresident and Fellows of Harvard College
InventorsDarren E. Higgins, Michael N. Starnbach, Todd Gierahn, Nadia R. Roan
Life of this patent
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Abstract
Replicable libraries having discrete members in defined locations for screening for antigens to a pathogenic organism are provided. Also provided are methods for using such libraries as well as a specific antigen, CT788, which induces T-cell activation during a Chlamydia infection.
Claims16
An epitope cocktail comprising (i) an immunologically effective amount of an adjuvant, and (ii) at least 5 epitopes identified using a method of determining whether a library contains or encodes an immunogenic polypeptide, wherein said library comprises at least 20 discrete members in defined locations and said members each comprise a cell or virus comprising a pre-determined open reading frame of a polynucleotide encoding a polypeptide, or a portion thereof, differentially expressed in a neoplastic cell as compared to a corresponding normal cell, said pre-determined open reading frame operably linked to a promoter,
- said method comprising:
- (a) individually contacting a member of said library with a second cell capable of (i) endocytosing said cell or said virus and (ii) displaying a polypeptide encoded by said pre-determined open reading frame on its surface through the major histocompatibility complex (MHC class) I pathway;
- (b) individually contacting each member of step (a) with a cytotoxic T lymphocyte (CTL) cell derived from a mammal having, or having previously had, a neoplasm;
- (c) detecting whether said CTL cell is activated, wherein activation of said CTL cell indicates that said member of said library contains said pre-determined open reading frame which encodes at least a portion of said immunogenic polypeptide;
- (d) identifying an epitope sufficient for CTL activation within said polypeptide, or portion thereof, determined to be immunogenic in step (c);
- and
- (e) formulating at least 5 epitopes identified in step (d) as an epitope cocktail;
- wherein the cocktail, upon administration to a subject, induces a cytotoxic T lymphocyte response to each of the at least 5 epitopes.
Dependencies are inferred from the claim text.