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Human IgE against the major allergen Bet v 1--defining an epitope with limited cross-reactivity between different PR-10 family proteins.

Levin M, Davies AM, Liljekvist M, Carlsson F, Gould HJ, Sutton BJ, Ohlin M - Clin. Exp. Allergy (2014)

Bottom Line: This provides a potential explanation, at the molecular level, for the differences in recognition of isoforms of Bet v 1 and other allergens in the PR-10 protein family displayed by IgE targeting this epitope.Finally, we present the first high-resolution structure of a human allergen-specific IgE fragment in the single-chain fragment variable (scFv) format.Such studies may aid us in development of better diagnostic tools and guide us in the development of new therapeutic compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.

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(a) Overall structure of the M0418 scFv. The disposition of CDRH3 above the surface of molecule A is shown, and the H and L chain V domains are coloured in salmon and white, respectively. (b) CDRH3 from molecule A. A 2Fo-Fc electron density map is contoured at 1.0σ around residues from CDRH3. Two symmetry-related copies of molecule B (pink and green) flank CDRH3 on either side. Residues from CDRH3 molecule A are shown as a stick representation, as are selected residues from the two symmetry-related molecules, and the two alternative conformations modelled for Leu107 (VH) and Ser92 (VL) are also shown. A hydrogen bond between Tyr114 (VH) Arg95 (VL) is indicated with a black line. The figure was produced with PyMOL 42.
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fig05: (a) Overall structure of the M0418 scFv. The disposition of CDRH3 above the surface of molecule A is shown, and the H and L chain V domains are coloured in salmon and white, respectively. (b) CDRH3 from molecule A. A 2Fo-Fc electron density map is contoured at 1.0σ around residues from CDRH3. Two symmetry-related copies of molecule B (pink and green) flank CDRH3 on either side. Residues from CDRH3 molecule A are shown as a stick representation, as are selected residues from the two symmetry-related molecules, and the two alternative conformations modelled for Leu107 (VH) and Ser92 (VL) are also shown. A hydrogen bond between Tyr114 (VH) Arg95 (VL) is indicated with a black line. The figure was produced with PyMOL 42.

Mentions: The crystal structure of the M0418 scFv was determined to 1.3Å resolution. The structures of the two independent molecules of the asymmetric unit were similar and were superposed with an RMSD value of 0.56Å over 232 Cα atoms. The most significant difference between the two molecules was disorder of a stretch of residues from CDRH3 of molecule B (residues 110-112.3), while that from molecule A was completely modelled. In molecule A, CDRH3 extends ˜8Å above the surface of the scFv (Fig.5a).


Human IgE against the major allergen Bet v 1--defining an epitope with limited cross-reactivity between different PR-10 family proteins.

Levin M, Davies AM, Liljekvist M, Carlsson F, Gould HJ, Sutton BJ, Ohlin M - Clin. Exp. Allergy (2014)

(a) Overall structure of the M0418 scFv. The disposition of CDRH3 above the surface of molecule A is shown, and the H and L chain V domains are coloured in salmon and white, respectively. (b) CDRH3 from molecule A. A 2Fo-Fc electron density map is contoured at 1.0σ around residues from CDRH3. Two symmetry-related copies of molecule B (pink and green) flank CDRH3 on either side. Residues from CDRH3 molecule A are shown as a stick representation, as are selected residues from the two symmetry-related molecules, and the two alternative conformations modelled for Leu107 (VH) and Ser92 (VL) are also shown. A hydrogen bond between Tyr114 (VH) Arg95 (VL) is indicated with a black line. The figure was produced with PyMOL 42.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215112&req=5

fig05: (a) Overall structure of the M0418 scFv. The disposition of CDRH3 above the surface of molecule A is shown, and the H and L chain V domains are coloured in salmon and white, respectively. (b) CDRH3 from molecule A. A 2Fo-Fc electron density map is contoured at 1.0σ around residues from CDRH3. Two symmetry-related copies of molecule B (pink and green) flank CDRH3 on either side. Residues from CDRH3 molecule A are shown as a stick representation, as are selected residues from the two symmetry-related molecules, and the two alternative conformations modelled for Leu107 (VH) and Ser92 (VL) are also shown. A hydrogen bond between Tyr114 (VH) Arg95 (VL) is indicated with a black line. The figure was produced with PyMOL 42.
Mentions: The crystal structure of the M0418 scFv was determined to 1.3Å resolution. The structures of the two independent molecules of the asymmetric unit were similar and were superposed with an RMSD value of 0.56Å over 232 Cα atoms. The most significant difference between the two molecules was disorder of a stretch of residues from CDRH3 of molecule B (residues 110-112.3), while that from molecule A was completely modelled. In molecule A, CDRH3 extends ˜8Å above the surface of the scFv (Fig.5a).

Bottom Line: This provides a potential explanation, at the molecular level, for the differences in recognition of isoforms of Bet v 1 and other allergens in the PR-10 protein family displayed by IgE targeting this epitope.Finally, we present the first high-resolution structure of a human allergen-specific IgE fragment in the single-chain fragment variable (scFv) format.Such studies may aid us in development of better diagnostic tools and guide us in the development of new therapeutic compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunotechnology, Lund University, Lund, Sweden.

Show MeSH
Related in: MedlinePlus