Antigens

Abstract

Any molecule ranging from simple chemical compounds to complex macromolecules, which are capable of being recognised by one or more constituents of the innate and adaptive immune system, is called an ‘antigen’. In the innate immune system, antigens are the pathogen‐associated molecular patterns recognised by the pattern recognition receptors expressed on macrophages, dendritic cells and NK cells. NK cells express an array of additional sets of receptors that recognise unconventional antigens. In the adaptive immune system, the B‐lymphocyte‐expressed immunoglobulin and T‐lymphocyte‐expressed T cell receptor recognise either specific conformation on the antigen or the amino acid sequence in the peptide, respectively. The antigens, which induce tolerogenic response or an allergic response, are called tolerogens or allergens, respectively. However, all antigens do not necessarily elicit antigen‐specific immune responses; those eliciting an immune response are termed immunogens. So, antigenicity of a molecule refers to its capacity to be recognised by the immune receptors, whereas immunogenicity is its ability to induce an immune response. Thus, all immunogens are antigens but all antigens are not immunogens.

Key Concepts

  • Antigens are those molecules that are specifically recognised by the receptors of the innate and adaptive immune systems.
  • Immunogens are those molecules that are able to elicit immune responses with negative or positive effects such that immune responses are suppressed or activated, respectively. The immunogens that lead to suppression or tolerance to the immune system are called tolerogens. The immunogens that cause allergic immune response are called allergens.
  • Haptens are small molecules that are able to bind antibodies but are unable to evoke an antibody response. So, all immunogens are antigens but all antigens are not immunogens.
  • Toll‐like receptors – 12 in mouse but 10 in human – in the innate immune system recognise many patterns on antigens. Two different toll‐like receptors can combine to increase the coverage of pathogen‐associated molecular patterns recognition.
  • Natural killer (NK) cells are innate immune cells which express an array of unique germ‐line‐encoded nonrearranging receptors that recognise unconventional antigens.
  • Recognition with finer antigenic specificity is executed by immunoglobulin and T‐lymphocyte receptors in the adaptive immune system.
  • The ability to rearrange the genes of the receptors (B‐ and T‐cell receptor) in the adaptive immune system creates a huge repertoire of antigen specificity, whereas such a feature is not available with the receptors of the innate immune system.
  • Recognition of specific antigen links the recall response to antigen‐specific memory, which is a characteristic of the adaptive, but not the innate, immune system.
  • B‐cell receptors recognise virtually any antigens in a conformation‐dependent manner and do not need any processing of the antigen for its recognition, whereas the T‐cell receptor recognition of an antigen depends primarily on the sequence of amino acids in the peptide.
  • T‐cell receptors recognise primarily peptide antigens in association with major histocompatibility complex molecules that necessitate processing of the antigens before the recognition. NK T cells recognise glycolipid antigens in the context of CD1d, an MHC‐like nonpolymorphic molecule on antigen‐presenting cells.

Keywords: adaptive immunity; antigenicity; epitopes; immune recognition; antigen receptors; pattern recognition receptors; pathogen‐associated molecular patterns

Figure 1. Antigen classification. (a) All antigens do not elicit immune response. Those which induce tolerance are called tolerogens. Small molecules which cannot elicit immune response on their own are termed haptens. These haptens can evoke immune response when conjugated to a carrier protein (b). The antigens which can trigger immune response are called immunogens. Among the immunogens, some molecules can result in allergic immune response following sensitisation. These molecules are called allergens. So, all immunogens are antigens but all antigens are not necessarily immunogens.
Figure 2. Antibody binding to a protein antigen. The figure shows a cartoon of a folded protein with differently shaded residues, as numbered. Antibodies can bind the epitope formed by the residues 21, 135 and 147 or the epitope formed by 87, 88, 89 and 90. The former epitope is called noncontiguous epitope, whereas the latter is called a contiguous epitope.
Figure 3. T cells recognise a peptide through TCR–peptide–MHC ternary complex. A peptide antigen (P) is selected and complexed to an MHC molecule forming a peptide–MHC complex during antigen processing. The peptide bound by α1 and β1 domains of MHC‐II is recognised by a combination of α and β chains of TCR. The MHC‐II also binds the TCR.
close

References

Ahlers JD and Belyakov IM (2010) Molecular pathways regulating CD4(+) T cell differentiation, anergy and memory with implications for vaccines. Trends in Molecular Medicine 16: 478–491.

Bergman Y and Cedar H (2004) A stepwise epigenetic process controls immunoglobulin allelic exclusion. Nature Reviews Immunology 4: 753–761.

Bjorkman PJ, Saper MA, Samraoui B, et al. (1987) The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329: 512–518.

Bjorkman PJ (2015) Not second class: the first class II MHC crystal structure. Journal of Immunology 194: 3–4.

Bridgeman JS, Sewell AK, Miles JJ, Price DA and Cole DK (2012) Structural and biophysical determinants of αβ T‐cell antigen recognition. Immunology 135: 9–18.

Brown AR (1992) Immunological functions of splenic B‐lymphocytes. Critical Reviews in Immunology 11: 395–417.

Butler JE, Zhao Y, Sinkora M, Wertz N and Kacskovics I (2009) Immunoglobulins, antibody repertoire and B cell development. Developmental & Comparative Immunology 33: 321–333.

Caoili SE (2006) A structural‐energetic basis for B‐cell epitope prediction. Protein & Peptide Letters 13: 743–751.

Chen S, Li Y, Depontieu FR, et al. (2013) Structure‐based design of altered MHC class II‐restricted peptide ligands with heterogeneous immunogenicity. Journal of Immunology 191: 5097–5106.

Chien YH and Konigshofer Y (2007) Antigen recognition by gammadelta T cells. Immunology Reviews 215: 46–58.

Crotty S (2011) Follicular helper CD4 T cells (TFH). Annual Review of Immunology 29: 621–663.

Deng L and Mariuzza RA (2006) Structural basis for recognition of MHC and MHC‐like ligands by natural killer cell receptors. Seminars in Immunology 18: 159–166.

Di Noia JM and Neuberger MS (2007) Molecular mechanisms of antibody somatic hypermutation. Annual Review of Biochemistry 76: 1–22.

Dunkley ML, Husband AJ and Underdown BJ (1990) Cognate T‐cell help in the induction of IgA responses in vivo. Immunology 71: 16–19.

Germain RN (2004) An innately interesting decade of research in immunology. Nature Medicine 10: 1307–1320.

Imler JL and Hoffmann JA (2000) Toll and Toll‐like proteins: an ancient family of receptors signaling infection. Reviews in Immunogenetics 2: 294–304.

Imler JL and Hoffmann JA (2001) Toll receptors in innate immunity. Trends in Cell Biology 11: 304–311.

Kantor AB and Herzenberg LA (1993) Origin of murine B cell lineages. Annual Review of Immunology 11: 501–538.

Kumar H, Kawai T and Akira S (2011) Pathogen recognition by the innate immune system. International Reviews of Immunology 30: 16–34.

Lanier LL (2005) NK cell recognition. Annual Review of Immunology 23: 225–274.

Lazarski CA, Chaves FA, Jenks SA, et al. (2005) The kinetic stability of MHC class II: peptide complexes is a key parameter that dictates immunodominance. Immunity 23: 29–40.

Maizels N (2005) Immunoglobulin gene diversification. Annual Review of Genetics 39: 23–46.

McCoy CE and O'Neill LA (2008) The role of toll‐like receptors in macrophages. Frontiers in Bioscience 13: 62–70.

van der Merwe PA and Davis SJ (2003) Molecular interactions mediating T cell antigen recognition. Annual Review of Immunology 21: 659–684.

Meyer C, Zeng X and Chien YH (2010) Ligand recognition during thymic development and gammadelta T cell function specification. Seminars in Immunology 22: 207–213.

Nikoopour E and Singh B (2014) Reciprocity in microbiome and immune system interactions and its implications in disease and health. Inflammation & Allergy‐Drug Targets 13: 94–104.

Nishimura Y, Chen Y‐Z, Kanai T, et al. (1998) Modification of human T‐cell responses by altered peptide ligands: a new approach to antigen‐specific modification. Internal Medicine 37: 804–817.

O'Hehir RE, Garman RD, Greenstein JL and Lamb JR (1991) The specificity and regulation of T‐cell responsiveness to allergens. Annual Review of Immunology 9: 67–95.

Pink JR (1990) A comment on allelic exclusion, ‘D‐disaster’ and germ‐line gene specificities. Immunology Reviews 115: 239–241.

Quintin J and Levitz SM (2013) NKp30 enables NK cells to act naturally with fungi. Cell Host & Microbe 14: 369–371.

Raulet DH and Vance RE (2006) Self‐tolerance of natural killer cells. Nature Reviews Immunology 6: 520–531.

Rothenberg EV (2014) Transcriptional control of early T and B cell developmental choices. Annual Review of Immunology 32: 283–321.

Rudolph MG, Luz JG and Wilson IA (2002) Structural and thermodynamic correlates of T cell signaling. Annual Review of Biophysics and Biomolecular Structure 31: 121–149.

Rudolph MG, Stanfield RL and Wilson IA (2006) How TCRs bind MHCs, peptides, and coreceptors. Annual Review of Immunology 24: 419–466.

Schirrmacher V and Rajewsky K (1970) Determination of antibody class in a system of cooperating antigenic determinants. Journal of Experimental Medicine 132: 1019–1034.

Schutze MP, Deriaud E, Przewlocki G and LeClerc C (1989) Carrier‐induced epitopic suppression is initiated through clonal dominance. Journal of Immunology 142: 2635–2640.

Schwartz RH (2003) T cell anergy. Annual Review of Immunology 21: 305–334.

Sela M (1973) The Antigens (Vol I – VII). New York: Academic Press.

Silverstein AM (1979) History of immunology. Cellular versus humoral immunity: determinants and consequences of an epic 19th century battle. Cellular Immunology 48: 208–221.

Silverstein AM (2003) Cellular versus humoral immunology: a century‐long dispute. Nature Immunology 4: 425–428.

Slifka MK, Blattman JN, Sourdive DJ, et al. (2003) Preferential escape of subdominant CD8+ T cells during negative selection results in an altered antiviral T cell hierarchy. Journal of Immunology 170: 1231–1239.

Sun P, Ju H, Liu Z, et al. (2013) Bioinformatics resources and tools for conformational B‐cell epitope prediction. Computational and Mathematical Methods in Medicine 2013: 943636.

Tan SY and Dee MK (2009) Elie Metchnikoff (1845‐1916): discoverer of phagocytosis. Singapore Medical Journal 50: 456–457.

Tonegawa S (1983) Somatic generation of antibody diversity. Nature 302: 575–581.

Vazquez MI, Catalan‐Dibene J and Zlotnik A (2015) B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine 74: 318–326.

Victora GD and Nussenzweig MC (2012) Germinal centers. Annual Review of Immunology 30: 429–457.

Weiner HL, Friedman A, Miller A, et al. (1994) Oral tolerance: immunologic mechanisms and treatment of animal and human organ‐specific autoimmune diseases by oral administration of autoantigens. Annual Review of Immunology 12: 809–837.

Yin L, Scott‐Browne J, Kappler JW, Gapin L and Marrack P (2012) T cells and their eons‐old obsession with MHC. Immunology Reviews 250: 49–60.

Zhu J, Yamane H and Paul WE (2010) Differentiation of effector CD4 T cell populations. Annual Review of Immunology 28: 445–489.

Zubler RH (2001) Naive and memory B cells in T‐cell‐dependent and T‐independent responses. Springer Seminars in Immunopathology 23: 405–419.

Further Reading

Arancibia SA, Beltrán CJ, Aguirre IM, et al. (2007) Toll‐like receptors are key participants in innate immune responses. Biological Research 40: 97–112.

Carreno LJ, Kharkwal SS and Porcelli SA (2014) Optimizing NKT cell ligands as vaccine adjuvants. Immunotherapy 6: 309–320.

Colman PM (1988) Structure of antigen–antibody complexes: implications for immune recognition. Advances in Immunology 43: 99–131.

Deng L and Mariuzza RA (2006) Structural basis for recognition of MHC and MHC‐like ligands by natural killer cell receptors. Seminars in Immunology 18: 159–166.

Ford ML and Evavold BD (2004) Degenerate recognition of T cell epitopes: impact of T cell receptor reserve and stability of peptide‐MHC complexes. Molecular Immunology 40: 1019–1025.

Jorgensen JL, Reay PA, Ehrich EW and Davis MM (1992) Molecular components of T‐cell recognition. Annual Review of Immunology 10: 835–873.

Kirkham CL and Carlyle JR (2014) Complexity and diversity of the NKR‐P1: Clr (Klrb1:Clec2) recognition systems. Frontiers in Immunology 5: article 214 (1–16).

Klein J (1997) Natural History of the Major Histocompatibility Complex, 2nd edn. New York: Wiley.

Klein J and Horejsi V (1997) Immunology, 2nd edn. Oxford: Blackwell Science.

Kruse PH, Matta J, Ugolini S and Vivier E (2014) Natural cytotoxicity receptors and their ligands. Immunology and Cell Biology 92: 221–229.

Moudgil KD and Sercarz EE (2005) Understanding crypticity is the key to revealing the pathogenesis of autoimmunity. Trends in Immunology 26: 355–359.

Novotny J, Handschumaker M and Bruccoleri RE (1987) Protein antigenicity: a static surface property. Immunology Today 8: 26–31.

Paul WE (ed) (2003) Fundamental Immunology, 5th (7th edn, 2012) edn. New York/Philadelphia: Raven Press/Lippincott, Williams and Wilkins.

Sadegh‐Nasseri S, Dalai SK, Korb Ferris LC and Mirshahidi S (2009) Suboptimal engagement of the T‐cell receptor by a variety of peptide‐MHC ligands triggers T‐cell anergy. Immunology 129: 1–7.

Shifrin N, Raulet DR and Ardolino M (2014) NK cell self‐tolerance, responsiveness and missing self recognition. Seminars in Immunology 26: 138–144.

Tefit JN, Davies G and Serra V (2010) NKT cell responses to glycolipid antigens. Methods in Molecular Biology 626: 149–167.

van de Veerdonk FL, Kullberg BJ, van der Meer JW, Gow NA and Netea MG (2008) Host‐microbe interactions: innate pattern recognition of fungal pathogens. Current Opinion in Microbiology 11: 305–312.

Yin L, Dai S, Clayton G, et al. (2013) Recognition of self and altered self by T cells in autoimmunity and allergy. Protein & Cell 4: 8–16.

Zinkernagel RA (1997) The discovery of MHC restriction. Immunology Today 8: 14–17.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Saha, Bhaskar(Sep 2015) Antigens. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000499.pub3]