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The structural basis of repertoire shift in an immune response to phosphocholine.

Publication ,  Journal Article
Brown, M; Schumacher, MA; Wiens, GD; Brennan, RG; Rittenberg, MB
Published in: J Exp Med
June 19, 2000

The immune response to phosphocholine (PC)-protein is characterized by a shift in antibody repertoire as the response progresses. This change in expressed gene combinations is accompanied by a shift in fine specificity toward the carrier, resulting in high affinity to PC-protein. The somatically mutated memory hybridoma, M3C65, possesses high affinity for PC-protein and the phenyl-hapten analogue, p-nitrophenyl phosphocholine (NPPC). Affinity measurements using related PC-phenyl analogues, including peptides of varying lengths, demonstrate that carrier determinants contribute to binding affinity and that somatic mutations alter this recognition. The crystal structure of an M3C65-NPPC complex at 2.35-A resolution allows evaluation of the three light chain mutations that confer high-affinity binding to NPPC. Only one of the mutations involves a contact residue, whereas the other two have indirect effects on the shape of the combining site. Comparison of the M3C65 structure to that of T15, an antibody dominating the primary response, provides clear structural evidence for the role of carrier determinants in promoting repertoire shift. These two antibodies express unrelated variable region heavy and light chain genes and represent a classic example of the effect of repertoire shift on maturation of the immune response.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

June 19, 2000

Volume

191

Issue

12

Start / End Page

2101 / 2112

Location

United States

Related Subject Headings

  • Surface Properties
  • Phosphorylcholine
  • Molecular Sequence Data
  • Models, Molecular
  • Immunology
  • Immunologic Memory
  • Immunoglobulins
  • Hybridomas
  • Hemocyanins
  • Haptens
 

Citation

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MLA
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Brown, M., Schumacher, M. A., Wiens, G. D., Brennan, R. G., & Rittenberg, M. B. (2000). The structural basis of repertoire shift in an immune response to phosphocholine. J Exp Med, 191(12), 2101–2112. https://doi.org/10.1084/jem.191.12.2101
Brown, M., M. A. Schumacher, G. D. Wiens, R. G. Brennan, and M. B. Rittenberg. “The structural basis of repertoire shift in an immune response to phosphocholine.J Exp Med 191, no. 12 (June 19, 2000): 2101–12. https://doi.org/10.1084/jem.191.12.2101.
Brown M, Schumacher MA, Wiens GD, Brennan RG, Rittenberg MB. The structural basis of repertoire shift in an immune response to phosphocholine. J Exp Med. 2000 Jun 19;191(12):2101–12.
Brown, M., et al. “The structural basis of repertoire shift in an immune response to phosphocholine.J Exp Med, vol. 191, no. 12, June 2000, pp. 2101–12. Pubmed, doi:10.1084/jem.191.12.2101.
Brown M, Schumacher MA, Wiens GD, Brennan RG, Rittenberg MB. The structural basis of repertoire shift in an immune response to phosphocholine. J Exp Med. 2000 Jun 19;191(12):2101–2112.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

June 19, 2000

Volume

191

Issue

12

Start / End Page

2101 / 2112

Location

United States

Related Subject Headings

  • Surface Properties
  • Phosphorylcholine
  • Molecular Sequence Data
  • Models, Molecular
  • Immunology
  • Immunologic Memory
  • Immunoglobulins
  • Hybridomas
  • Hemocyanins
  • Haptens