CorpusHuman Anatomy

Antigen

Also known as: antigens, epitope, antigenic determinant, immunogen, hapten, superantigen, allergen

Any molecule that can be specifically bound by an antibody, B-cell receptor or T-cell receptor; the precise part that is recognised is the epitope, and an antigen able to provoke a response by itself is an immunogen.

Overview

Antigens may be proteins, polysaccharides, lipids, nucleic acids or small chemicals, and come from microbes (microbial antigens), the environment (allergens), other individuals (alloantigens such as ABO and HLA), tumours (tumour antigens) or the body itself (autoantigens). Each antigen usually carries many epitopes (antigenic determinants). B-cell epitopes are recognised on the native molecule and may be conformational (formed by amino acids brought together by folding) or linear; antibodies can recognise any chemical class. αβ T-cell epitopes are short linear peptides displayed on MHC molecules: ≈ 8–10 amino acids on MHC class I and ≈ 13–25 on class II.

Immunogenicity — the ability to induce a response — depends on foreignness, size (large molecules > 10 kDa are more immunogenic), chemical complexity, the ability to be processed and presented (proteins are the best immunogens), dose, route, the presence of adjuvants or danger signals, and the host's genes (especially HLA type). Haptens are small molecules (e.g. penicillin, nickel ions, urushiol from poison ivy) that are not immunogenic alone but become so after binding a carrier protein — the basis of many drug allergies and contact dermatitis. Protein antigens are T-dependent; polymeric antigens such as capsular polysaccharides can activate B cells without T-cell help (T-independent), giving mainly IgM and little memory.

Superantigens are microbial toxins (staphylococcal toxic shock syndrome toxin-1 and enterotoxins, streptococcal pyrogenic exotoxins) that bypass normal recognition by clamping MHC class II to the side of the TCR Vβ region outside the peptide groove, activating up to ≈ 20% of all T cells at once instead of the usual tiny fraction — producing a massive cytokine release.

Function

  • Serves as the target recognised by antibodies, B-cell receptors and (as peptide–MHC) T-cell receptors.
  • Induces immune responses (immunogens) or, in some circumstances, tolerance (tolerogens).

Clinical significance

Toxic shock syndrome

Superantigen-driven polyclonal T-cell activation (e.g. S. aureus TSST-1 with retained tampons or wound packing; group A streptococcus) causes high fever, diffuse erythematous rash with later desquamation, hypotension and multi-organ failure.

Tumour antigens and markers

Tumour-specific neoantigens from mutated proteins are targets of anti-tumour T cells and checkpoint-inhibitor therapy; tumour-associated antigens such as CEA, AFP, PSA and CA-125 are used as serum markers.

Test yourself

MHC class II molecules…
  1. Are expressed on all nucleated cells
  2. Present endogenous peptides to CD8 T cells
  3. Present exogenous peptides to CD4 T cells and are expressed mainly on antigen-presenting cells
  4. Consist of a heavy chain associated with β2-microglobulin

Answer: Present exogenous peptides to CD4 T cells and are expressed mainly on antigen-presenting cells

Class II (HLA-DP, -DQ, -DR; α and β chains) is expressed on dendritic cells, macrophages, B cells and thymic epithelium and presents peptides from endocytosed (exogenous) proteins to CD4 T cells. Class I (heavy chain + β2-microglobulin) is on all nucleated cells and presents to CD8 cells.

Microfold (M) cells, which transport luminal antigens to underlying lymphoid follicles, are found in the…
  1. Follicle-associated epithelium over Peyer patches
  2. Germinal centres of lymph nodes
  3. Splenic red pulp
  4. Thymic medulla

Answer: Follicle-associated epithelium over Peyer patches

M cells in the follicle-associated epithelium of Peyer patches (and other MALT) lack a thick glycocalyx and microvilli and transcytose antigens to dendritic cells and lymphocytes in the subepithelial dome. Salmonella Typhi and poliovirus exploit them.

More lymphatic & immune system questions

Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.