Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein- receptor interaction

S. Fantappie, A. Corsini, A. Sidoli, P. Uboldi, A. Granata, T. Zanelli, P. Rossi, S. Marcovina, R. Fumagalli, A. L. Catapano

Research output: Contribution to journalArticle

Abstract

We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with β-galactosidase-apoB fusion proteins spanning different areas of the apoB- 100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.

Original languageEnglish
Pages (from-to)1111-1121
Number of pages11
JournalJournal of Lipid Research
Volume33
Issue number8
Publication statusPublished - 1992

Fingerprint

Apolipoprotein B-100
LDL Receptors
LDL Lipoproteins
Monoclonal Antibodies
Epitopes
Apolipoproteins B
Amino Acids
Apolipoprotein B-48
Galactosidases
Immunoglobulin Fab Fragments
Antibodies
Fibroblasts
Conformations
Fusion reactions
Proteins

Keywords

  • β-galactosidase-apoB fusion proteins
  • apoB receptor binding domain
  • apoB-100 thrombolytic fragments

ASJC Scopus subject areas

  • Endocrinology

Cite this

Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein- receptor interaction. / Fantappie, S.; Corsini, A.; Sidoli, A.; Uboldi, P.; Granata, A.; Zanelli, T.; Rossi, P.; Marcovina, S.; Fumagalli, R.; Catapano, A. L.

In: Journal of Lipid Research, Vol. 33, No. 8, 1992, p. 1111-1121.

Research output: Contribution to journalArticle

Fantappie, S, Corsini, A, Sidoli, A, Uboldi, P, Granata, A, Zanelli, T, Rossi, P, Marcovina, S, Fumagalli, R & Catapano, AL 1992, 'Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein- receptor interaction', Journal of Lipid Research, vol. 33, no. 8, pp. 1111-1121.
Fantappie, S. ; Corsini, A. ; Sidoli, A. ; Uboldi, P. ; Granata, A. ; Zanelli, T. ; Rossi, P. ; Marcovina, S. ; Fumagalli, R. ; Catapano, A. L. / Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein- receptor interaction. In: Journal of Lipid Research. 1992 ; Vol. 33, No. 8. pp. 1111-1121.
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abstract = "We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with β-galactosidase-apoB fusion proteins spanning different areas of the apoB- 100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95{\%}) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.",
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T1 - Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein- receptor interaction

AU - Fantappie, S.

AU - Corsini, A.

AU - Sidoli, A.

AU - Uboldi, P.

AU - Granata, A.

AU - Zanelli, T.

AU - Rossi, P.

AU - Marcovina, S.

AU - Fumagalli, R.

AU - Catapano, A. L.

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N2 - We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with β-galactosidase-apoB fusion proteins spanning different areas of the apoB- 100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.

AB - We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with β-galactosidase-apoB fusion proteins spanning different areas of the apoB- 100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.

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