Kinetic evidence for hapten-induced conformational transition in immunoglobin MOPC 460.

Lancet, Doron; Pecht, Israel

doi:10.1073/pnas.73.10.3549

Cited by 91 publications

(47 citation statements)

References 19 publications

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“…An alternative selective explanation termed "preexisting equilibrium" posits that two antibody conformations-one abundant, one rareexist in equilibrium when not bound to antigen. Antigen binds selectively to the rare conformation, whose free concentration is maintained by reequilibration from the pool of unbound antibody (5). When an antibodyantigen complex undergoes crystallization, the rare antibody isomer is preferentially observed; when uncomplexed antibody is crystallized, the abundant form is preferentially observed (the same structural data are obtained with both mechanisms).…”

supporting

confidence: 62%

“…For instance, the TEOSINTE BRANCHED gene of corn limits the outgrowth of side branches (4) imbuing corn plants with their upright and unbranched growth habit, a boon to agriculturalists. Similarly, the CYCLOIDEA gene of snapdragon limits growth of a subset of petals in the snapdragon flower resulting in the flower's asymmetric shape (5), which enables insect pollinators to do their job.…”

Section: Isomeric Antibodiesmentioning

confidence: 99%

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Isomeric Antibodies

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2003

Science

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supporting

confidence: 62%

Section: Isomeric Antibodiesmentioning

confidence: 99%

Isomeric Antibodies

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2003

Science

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“…Carried out initially with a myeloma protein that recognized a DNP amino acid (36) and then with mAbs to phenyloxazolone (37), association rates could not be fit to a single exponential function in the myeloma protein and in 10-20% of the antihapten mAbs. Multiphasic kinetics with up to three stages were observed (28).…”

Section: Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

Evolving concepts of specificity in immune reactions

Eisen

Chakraborty

2010

Proc. Natl. Acad. Sci. U.S.A.

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Our goal is to provide a perspective on current understanding of the origins of specificity in immune reactions, a topic that has intrigued scientists for over a century. A fundamental property of adaptive immune responses is the ability to discriminate among an immense variety of substances by means of antibodies (Abs) and Ab-like receptors on T lymphocytes [T-cell receptors (TCRs)], each able to bind a particular chemical structure [the antigen (Ag)] and not, or only weakly, similar alternatives. Evidence has long existed, however, and has grown, especially recently, that while exhibiting remarkable specificity, many individual Abs and TCRs can also bind a variety of very different ligands. How can Ag recognition by these receptors exercise the great specificity for which they are renowned and yet react with a variety of different ligands (degeneracy)? We critically consider the mechanistic bases for this specificity/degeneracy enigma and also compare and contrast Ag recognition by Abs and TCRs.T cells | peptide-MHC complexes | receptor-ligand interactions | antibody isomerism

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“…The Fab fragment of protein MOPC 460 was prepared as described by Lancet & Pecht (1976). Dinitronaphthol was obtained from Koch-Light Laboratories, Colnbrook, Bucks.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the dimensions of the combining sites of the dinitrophenyl-binding immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 by spin-label mapping

Willan

Marsh

Sunderland

et al. 1977

Biochemical Journal

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The mouse immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 all possess dinitrophenyl (Dnp)-binding activity. Differences in specificities were shown by measuring the affinities of a variety of haptens. By using a series of Dnp-spin-labelled haptens, the dimensions of the binding sites of the three myeloma proteins were compared by the method described for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem. J.165, 177-197]. The dinitrophenyl ring is rigidly held in all three sites. The depths of the sites are all 1.1-1.2nm, but there are differences in the lateral dimensions at the entrance to the sites. For protein XRPC 25 these dimensions are 0.75nmx0.8nm, which may be compared with 0.85nmx1.1nm for protein MOPC 315 and >/=1.0nmx1.1nm for protein MOPC 460. The site in protein MOPC 460 is more symmetrical with respect to the plane of the dinitrophenyl ring than in either of the other two myeloma proteins and also allows greater penetration of solvent. In protein XRPC 25 a positively charged residue was located at the entrance to the site, similarly positioned to that reported for protein MOPC 315 [Sutton, Gettins, Givol, Marsh, Wain-Hobson, Willan & Dwek (1977) Biochem.J.165, 177-197]. All three proteins possess lanthanide-binding sites, but only in protein MOPC 315 is there antagonism between lanthanide and hapten binding. However, the effects of the diamagnetic La(III) on the electron-spin-resonance spectra of bound Dnp spin labels in both proteins MOPC 460 and XRPC 25 suggest an interaction between the two sites. Comparison of this effect with that caused by the addition of the paramagnetic Gd(III) enables the distance between the lanthanide- and hapten-binding sites to be calculated. In both proteins MOPC 460 and MOPC 315 the metal site is approx. 1.0nm from the nitroxide moiety of the spin-labelled hapten, but in protein XRPC 25 this distance is at least 2.0nm.

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Kinetic evidence for hapten-induced conformational transition in immunoglobin MOPC 460.

Cited by 91 publications

References 19 publications

Isomeric Antibodies

Isomeric Antibodies

Evolving concepts of specificity in immune reactions

Comparison of the dimensions of the combining sites of the dinitrophenyl-binding immunoglobulin A myeloma proteins MOPC 315, MOPC 460 and XRPC 25 by spin-label mapping

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