About anti-hapten antibodies

Anti-hapten IgGs are in wide use. For example, anti-BrdU and anti-digoxigen IgGs are common anti-hapten reagents. In the 1930’s, Karl Landsteiner [1] showed that antibodies can even distinguish cis-trans isomers of small molecules. His demonstrations of regio- and stereospecific binding of small molecules by IgGs long remained unexploited in cellular mapping, but discrimination of even enantiomers (e.g. D- and L-aspartate) is now routine [2, 3, 4]. Hapten immunochemistry forms the basis of a massive clinical, forensic and environmental testing industry. Targeting free aromatic [5, 6] and aliphatic amines [7, 2, 8, 9-15] to probe cellular expression patterns has also become standard in neurobiology. Few molecules are resistant to hapten detection methods. Even exotic polymeric targets such as C60 fullerenes, targets as nonpolar as cholesterol, or as large as vitamin B12 have been haptenized [16-18]. All biologically relevant small molecules are potential haptens.


  1. Landsteiner, K., The specificity of serological reactions. 1936, Springfield: Charles C. Thomas.
  2. Marc, R.E., R.F. Murry, and S.F. Basinger, Pattern recognition of amino acid signatures in retinal neurons. Journal of Neuroscience, 1995. 15(7 Pt 2): p. 5106-29.
  3. Gundersen, V., et al., Demonstration of Glutamate/Aspartate Uptake Activity in Nerve-Endings by Use of Antibodies Recognizing Exogenous D-Aspartate. Neuroscience, 1993. 57(1): p. 97-111.
  4. Pow, D.V. and D.K. Crook, Direct immunocytochemical evidence for the transfer of glutamine from glial cells to neurons: Use of specific antibodies directed against the D-stereoisomers of glutamate and glutamine. Neuroscience, 1996. 70(1): p. 295-302.
  5. Geffard, M., P. Segula, and A.M. Heinrich-Rock, Antisera against catecholamines: specificity studies and physicochemical data for anti-dopamine and anti-p-tyramine antibodies. Molecular Immunology, 1984. 21: p. 515-522.
  6. Steinbusch, H.W.M., et al., Immunohistochemical localization of monoamines and cyclic nucleotides. Acta Histochem, 1988. S35: p. 85-106.
  7. Marc, R.E. and B.W. Jones, Molecular phenotyping of retinal ganglion cells. Journal of Neuroscience, 2002. 22: p. 412-427.
  8. Storm-Mathisen, J., et al., 1st Visualization of Glutamate and GABA in Neurons by Immunocytochemistry. Nature, 1983. 301(5900): p. 517-520.
  9. Pow, D.V., Immunocytochemistry of Amino-Acids in the Rodent Pituitary Using Extremely Specific, Very High-Titer Antisera. Journal of Neuroendocrinology, 1993. 5(4): p. 349-356.
  10. Pow, D.V. and D.K. Crook, Extremely High-Titer Polyclonal Antisera against Small Neurotransmitter Molecules - Rapid Production, Characterization and Use in Light-Microscopic and Electron-Microscopic Immunocytochemistry. Journal of Neuroscience Methods, 1993. 48(1-2): p. 51-63.
  11. Kalloniatis, M., R.E. Marc, and R.F. Murry, Amino acid signatures in the primate retina. Journal of Neuroscience, 1996. 16(21): p. 6807-29.
  12. Marc, R.E., et al., Amino acid signatures in the normal cat retina. Investigative Ophthalmology & Visual Science, 1998. 39(9): p. 1685-93.
  13. Ottersen, O.P. and J. Stormmathisen, Glutamate-Containing and Gaba-Containing Neurons in the Mouse and Rat-Brain, as Demonstrated with a New Immunocytochemical Technique. Journal of Comparative Neurology, 1984. 229(3): p. 374-392.
  14. Ottersen, O.P. and J. Stormmathisen, Different Neuronal Localization of Aspartate-Like and Glutamate-Like Immunoreactivities in the Hippocampus of Rat, Guinea-Pig and Senegalese Baboon (PapioPapio), with a Note on the Distribution of Gamma-Aminobutyrate. Neuroscience, 1985. 16(3): p. 589.
  15. Storm-Mathisen, J. and O.P. Ottersen, Immunocytochemistry of Glutamate at the Synaptic Level. Journal of Histochemistry & Cytochemistry, 1990. 38(12): p. 1733-1743.
  16. Izhaky, D. and I. Pecht, What else can the immune system recognize? Proc. Natl. Acad. Sci., 1998. 95: 11509-11510
  17. Chen, B.-X., et al., Antigenicity of fullerenes: Antibodies specific for fullerenes and their characteristics. Proc. Natl. Acad. Sci., 1998. 95: p. 10809-10813.
  18. Birn, H., et al., Megalin is essential for renal proximal tubule reabsorption and accumulation of transcobalamin-B12. Am J Physiol Renal Physiol, 2002. 282: p. F408-F416.