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Structural and thermodynamic approach to peptide immunogenicity

Camacho, CJ and Katsumata, Y and Ascherman, DP (2008) Structural and thermodynamic approach to peptide immunogenicity. PLoS Computational Biology, 4 (11). ISSN 1553-734X

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Abstract

In the conventional paradigm of humoral immunity, B cells recognize their cognate antigen target in its native form. However, it is well known that relatively unstable peptides bearing only partial structural resemblance to the native protein can trigger antibodies recognizing higher-order structures found in the native protein. On the basis of sound thermodynamic principles, this work reveals that stability of immunogenic protein-like motifs is a critical parameter rationalizing the diverse humoral immune responses induced by different linear peptide epitopes. In this paradigm, peptides with a minimal amount of stability (ΔGX<0 kcal/mol) around a proteinlike motif (X) are capable of inducing antibodies with similar affinity for both peptide and native protein, more weakly stable peptides (ΔG X>0 kcal/mol) trigger antibodies recognizing full protein but not peptide, and unstable peptides (ΔGX>8 kcal/mol) fail to generate antibodies against either peptide or protein. Immunization experiments involving peptides derived from the autoantigen histidyl-tRNA synthetase verify that selected peptides with varying relative stabilities predicted by molecular dynamics simulations induce antibody responses consistent with this theory. Collectively, these studies provide insight pertinent to the structural basis of immunogenicity and, at the same time, validate this form of thermodynamic and molecular modeling as an approach to probe the development/evolution of humoral immune responses. © 2008 Camacho et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Camacho, CJccamacho@pitt.eduCCAMACHO
Katsumata, Y
Ascherman, DP
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLengauer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 November 2008
Date Type: Publication
Journal or Publication Title: PLoS Computational Biology
Volume: 4
Number: 11
DOI or Unique Handle: 10.1371/journal.pcbi.1000231
Schools and Programs: School of Medicine > Computational Biology
Refereed: Yes
ISSN: 1553-734X
PubMed Central ID: PMC2577884
PubMed ID: 19023401
Date Deposited: 24 Jul 2012 18:53
Last Modified: 22 Jan 2019 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/13094

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