Heavy chain antibodies

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Heavy chain antibodies are antibodies that consist entirely of heavy chains . They differ structurally from conventional IgG antibodies , which are made up of two heavy and two light chains . Heavy chain antibodies could only be found in nature within the class of cartilaginous fish and within the camel family in addition to conventional antibodies.

structure

Structure of heavy chain antibodies in cartilaginous fish (IgNAR) and camels (hcIgG) compared to conventional IgG antibodies

IgNAR of cartilaginous fish

Heavy chain antibodies in cartilaginous fish, also known as immunoglobulin new antigen receptor (IgNAR), differ structurally considerably from conventional antibodies in mammals. They consist of two heavy chains, each of which consists of five constant domains and one variable domain responsible for antigen recognition. The position of the disulfide bridges also differs from that of conventional antibodies. Within the antigen-binding variable domains, IgNARs differ from conventional IgG antibodies by a pronounced CDR3 loop.

IgG 2a / b and IgG 3 of camels

In addition to conventional IgG 1 antibodies, each consisting of two light and two heavy chains , members of the camel family also produce heavy chain antibodies of the IgG 2a , IgG 2b and IgG 3 types . These consist of two heavy chains, which in turn are made up of two constant domains and one variable domain.

Although it is assumed that the heavy chain antibodies of camels are not directly related to the IgNARs of gnarlfish, both antibody families show striking similarities which are attributed to convergent evolution . Both IgNARs and the camel heavy chain antibodies have a pronounced CDR3 loop, which is involved in antigen binding and has the ability to penetrate cleft structures that are inaccessible to conventional antibodies.

use

Thanks to their simple structure of the variable domains compared to conventional antibodies, heavy chain antibodies are of great interest in research and in the development of new drugs . Their variable domains, consisting of only one domain with a molar mass of only 12 to 15  kDa , are the smallest antibody fragments that are still capable of antigen binding. These fragments, which are also referred to as single domain antibodies , combine properties of low molecular weight substances and antibodies.

Individual evidence

  1. ↑ Conrath, HT et al .: Emergence and evolution of functional heavy-chain antibodies in Camelidae . In: Dev Comp Immunol . 27, No. 2, 2003, pp. 87-103. PMID 12543123 .
  2. ↑ Greenberg AS, Avila D, Hughes M, Hughes A, McKinney EC, Flajnik MF: A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks . In: Nature . 374, No. 6518, March 1995, pp. 168-73. doi : 10.1038 / 374168a0 . PMID 7877689 .
  3. ^ A b Stanfield RL, Dooley H, Flajnik MF, Wilson IA: Crystal structure of a shark single-domain antibody V region in complex with lysozyme . In: Science . 305, No. 5691, September 2004, pp. 1770-3. doi : 10.1126 / science.1101148 . PMID 15319492 .
  4. ↑ Hamers-Casterman C, Atarhouch T, Muyldermans S, et al. : Naturally occurring antibodies devoid of light chains . In: Nature . 363, No. 6428, June 1993, pp. 446-8. doi : 10.1038 / 363446a0 . PMID 8502296 .
  5. ↑ Harmsen MM, De Haard HJ: Properties, production, and applications of camelid single-domain antibody fragments . In: Appl. Microbiol. Biotechnol. . 77, No. 1, November 2007, pp. 13-22. doi : 10.1007 / s00253-007-1142-2 . PMID 17704915 . PMC 2039825 (free full text).

literature

  • Wesolowski J, Alzogaray V, Reyelt J, et al. : Single domain antibodies: promising experimental and therapeutic tools in infection and immunity . In: Med. Microbiol. Immunol. . 198, No. 3, August 2009, pp. 157-74. doi : 10.1007 / s00430-009-0116-7 . PMID 19529959 . PMC 2714450 (free full text).