Abstract
Mapping of antigenic peptide sequences from proteins of relevant pathogens recognized by T helper (Th) and by cytolytic T lymphocytes (CTL) is crucial for vaccine development. In fact, mapping of T-cell epitopes provides useful information for the design of peptide-based vaccines and of peptide libraries to monitor specific cellular immunity in protected individuals, patients and vaccinees. Nevertheless, epitope mapping is a challenging task. In fact, large panels of overlapping peptides need to be tested with lymphocytes to identify the sequences that induce a T-cell response. Since numerous peptide panels from antigenic proteins are to be screened, lymphocytes available from human subjects are a limiting factor. To overcome this limitation, high throughput (HTP) approaches based on miniaturization and automation of T-cell assays are needed. Here we consider the most recent applications of the HTP approach to T epitope mapping. The alternative or complementary use of in silico prediction and experimental epitope definition is discussed in the context of the recent literature. The currently used methods are described with special reference to the possibility of applying the HTP concept to make epitope mapping an easier procedure in terms of time, workload, reagents, cells and overall cost.
Highlights
Mapping of T epitopes on protein antigens derived from relevant pathogens implies the identification of amino acid sequences that are recognized by CD4 or CD8 T cells.The term “epitope” is frequently used interchangeably for “immunodominant peptide”
[1, 2] for several reasons: (1) epitopes are presented in the context of one or few MHC alleles [3,4,5,6,7] and in some instances they are promiscuous [8,9,10,11] or universal [12,13,14,15,16]; (2) epitopes represent the antigenic portion of a protein and the nonantigenic regions can be deleted; (3) epitopes restricted to different alleles can be collected to obtain selected peptide libraries that are recognized by the majority of the immune population [17, 18], thereby providing a valuable diagnostic tool [19,20,21,22,23,24,25,26,27]; (4) epitopes can be selected to construct peptide-based vaccines
This paper presents the conundrum of which should be the optimal overlap between contiguous peptides in order not to miss a stimulatory epitope
Summary
Mapping of T epitopes on protein antigens derived from relevant pathogens implies the identification of amino acid sequences that are recognized by CD4 or CD8 T cells. Selected peptide fragments can be assembled as mosaic proteins to produce polyvalent vaccines for coverage of potential T-cell epitopes in HIV variants. The converse situation, defined as deimmunization, permits selective removal by protein re-engineering of immunogenic epitopes identified on proteins to be used as therapeutic agents In this case, potential antigenicity must be avoided to improve clinical effectiveness. The HTP approach, permits reduction of the number of cells to be tested, of the amount of tested peptides, of the cost of reagents and of the workload referred to the information that can be obtained. The HTP concept can be applied to different techniques that can be automated and miniaturized, as described later
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