T Cell Epitopes:
T cell epitopes are displayed on the surface of antigen-presenting cells bound to major histocompatibility complex (MHC) molecules. In humans, specialized professional antigen-presenting cells display MHC class II peptides, while most nucleated somatic cells display MHC class I peptides. Peptides presented by MHC class I are generally 8-11 amino acids long, whereas those presented by MHC class II are longer, ranging from 13 to 17 amino acids. Additionally, non-classical MHC molecules present non-peptidic epitopes such as glycolipids.

B Cell Epitopes:
B-cell epitopes are regions on an antigen that bind to immunoglobulins or antibodies. These epitopes are primarily conformational and can also be categorized as either conformational or linear. Additional epitope types include cryptotopes, which are hidden when protein subunits aggregate, and neotopes, which are recognized only when in a specific quaternary structure and span multiple protein subunits. Neotopes are not recognized when the subunits separate.

Cross-reactivity

Epitopes may exhibit cross-reactivity, a feature leveraged by the immune system to regulate responses through anti-idiotypic antibodies, a concept proposed by Niels Kaj Jerne, a Nobel laureate. An antibody binding to an epitope can make its paratope a new epitope for another antibody, influencing immune response modulation depending on the class of the second antibody (IgM or IgG).

Epitope Mapping

T Cell Epitopes:
MHC class I and II epitopes can be predicted computationally, though the accuracy varies among algorithms. There are two primary approaches: data-driven, which predicts peptide-MHC binding based on sequences known to bind MHC molecules, and structure-based, which models the peptide-MHC structure but requires significant computational resources. Data-driven methods generally outperform structure-based methods.

B Cell Epitopes:
Epitope mapping can be conducted through structural studies using techniques like X-ray crystallography, nuclear magnetic resonance, and electron microscopy, or through functional studies using binding assays such as western blot, dot blot, and ELISA. Methods like high-throughput mutagenesis further facilitate rapid mapping of conformational epitopes on complex proteins.

Epitope Tags

Epitopes are crucial in proteomics for studying gene products. Using recombinant DNA, sequences coding for epitopes recognized by common antibodies can be fused to genes. This “epitope tag” allows antibodies to locate the protein, aiding in localization, purification, and characterization. Tags like Myc-tag, HA-tag, and FLAG-tag are commonly used.

Epitope-based Vaccines

The first epitope-based vaccine, introduced in 1985, utilizes isolated B-cell or T-cell epitopes to stimulate both humoral and cellular immune responses. These vaccines typically combine multiple epitopes to enhance efficacy, using in silico mapping to identify and engineer the epitopes for vaccine development. While generally safe, they can occasionally lead to adverse effects like cytokine storms.

Neoantigenic Determinants

A neoantigenic determinant is an epitope on a neoantigen, a new antigen not previously recognized by the immune system, often associated with tumor antigens in cancer cells. Neoantigens may arise from protein modifications like glycosylation or phosphorylation, creating new epitopes recognized by specific antibodies.