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Other meanings of Antigen

Immunology

Antigen

An antigen is any substance recognized by the adaptive immune system—typically as foreign—that triggers an immune response, such as the production of antibodies or activation of T cells.1 Most antigens are proteins or polysaccharides, but lipids, nucleic acids, and small molecules can also act as antigens when complexed with larger carriers.

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Main molecular classes
proteins, polysaccharides, lipids, nucleic acids
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T-cell recognition pathways
MHC class I (endogenous) and MHC class II (exogenous)
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Definition and core concept

Antigens are molecules that are specifically recognized by receptors of the adaptive immune system—either immunoglobulins (antibodies) on B cells or T-cell receptors (TCRs) on T cells—and that elicit an immune response.1 The term derives from antibody generator, reflecting the historical observation that these substances induce antibody formation. Antigens can be soluble molecules (e.g., toxins, pollen proteins) or surface structures on pathogens, cells, or particles. The portion of an antigen that is recognized by a receptor is called an epitope; a single antigen may contain multiple epitopes, each capable of binding a different antibody or TCR clone.

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Recognition and immune response

B cells recognize intact antigens directly via their membrane-bound antibodies, whereas T cells recognize peptide fragments of antigens bound to major histocompatibility complex (MHC) molecules on antigen-presenting cells.2 Two main processing pathways exist: endogenous antigens, such as viral proteins synthesized inside a cell, are presented on MHC class I to CD8+ cytotoxic T cells; exogenous antigens, taken up by phagocytosis, are processed and presented on MHC class II to CD4+ helper T cells. Cross-presentation allows dendritic cells to display exogenous antigens on MHC class I, enabling CD8+ responses to tumors and some vaccines. Full T-cell activation also requires co-stimulatory signals, without which antigen recognition leads to tolerance rather than immunity.

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Types and classifications

Antigens are classified by origin and function. Exogenous antigens enter the body from outside (e.g., bacterial proteins), while endogenous antigens are produced inside cells (e.g., viral proteins in infected cells). Autoantigens are self-molecules that become targets in autoimmune diseases; tumor antigens and neoantigens are mutated or overexpressed proteins on cancer cells. Superantigens, such as staphylococcal enterotoxins, bypass normal processing by cross-linking MHC class II molecules to TCR Vβ domains, causing massive polyclonal T-cell activation and cytokine storm. Haptens are small molecules that elicit an immune response only when conjugated to a carrier protein; for example, urushiol from poison ivy is a hapten that becomes antigenic after binding skin proteins.

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Lesser-known aspects and applications

Antigenic variation is a strategy used by pathogens to evade immunity: influenza viruses alter surface hemagglutinin and neuraminidase, and Trypanosoma brucei switches its variant surface glycoprotein coat.3 Epitope spreading—the broadening of the immune response to additional epitopes on the same antigen—can drive autoimmune disease progression. In diagnostics, antigens are the basis of enzyme-linked immunosorbent assays (ELISA) and rapid lateral-flow tests. Therapeutically, cancer vaccines target neoantigens to induce tumor-specific T-cell responses, and adjuvants like alum are used to enhance antigenicity.4 Conjugate vaccines link polysaccharide antigens to carrier proteins to elicit T-cell-dependent responses in infants.

Glossary

Epitope
The specific part of an antigen that is recognized by an antibody or T-cell receptor.
Hapten
A small molecule that becomes antigenic only when attached to a larger carrier protein.
Superantigen
A microbial toxin that causes non-specific activation of many T cells by cross-linking MHC and TCR molecules.
MHC (major histocompatibility complex)
Molecules that display peptide fragments for recognition by T cells.

The term 'antigen' is sometimes used loosely to include immunogens and tolerogens; strictly, an antigen is any molecule bound by immune receptors, whereas an immunogen elicits a response. This article focuses on the conventional sense of substances that trigger adaptive immune responses.