Characterization of antigenic peptide epitopes by reverse immunology: induction of cytotoxic T lymphocytes specific for exogenous peptide only

Characterization of antigenic peptide epitopes by reverse immunology: induction of cytotoxic T lymphocytes specific for exogenous peptide only

Characterization of antigenic peptide epitopes by reverse immunology: induction of cytotoxic T lymphocytes specific for exogenous peptide only

Abstract

Cytotoxic T lymphocytes (CTLs) recognize peptides derived
from endogenous antigen presented by MHC-class-I molecules
on the cell surface (Townsend and Bodmer, 1989). The detailed
molecular characterization of such epitopes is of considerable
interest, since synthetic peptides corresponding to epitopes encoded
by viral or tumor antigens can be used for targeted immunotherapy.
One strategy, referred to as ‘‘reverse immunology’’ (Boon
and Van der Bruggen, 1996), uses peptide-specific CTLs as a
read-out system for the presence of a peptide on the surface of
cells expressing endogenous antigen. In this approach, the
amino-acid sequence of the relevant antigen is screened for
peptides carrying the binding motif for the class-I molecule of
interest. CTLs specific for these peptides are then induced byin
vitro stimulation of CD81 T cells with appropriate peptide-pulsed
antigen-presenting cells (APCs). The ability of these CTLs to recognize processed peptide on the surface of cells expressing the class-Irestriction element and endogenous antigen reveals whether or not
the peptide is actually processed endogenously.

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