Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1.

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. Abstract Text:

Lili Huang,Motomu Shimaoka,Isaac J Rondon,Illa Roy,Qing Chang,Melody Po,Daniel T Dransfield,Robert C Ladner,Albert S B Edge,Azucena Salas,Clive R Wood,Timothy A Springer,Edward H Cohen,

LFA-1 (alpha(L)beta(2)) mediates cell-cell and cell-extracellular matrix adhesions essential for immune and inflammatory responses. One critical mechanism regulating LFA-1 activity is the conformational change of the ligand-binding alpha(L) I domain from low-affinity (LA), closed form, to the high-affinity (HA), open form. Most known integrin antagonists bind both forms. Antagonists specific for the HA alpha(L) I domain have not been described. Here, we report the identification and characterization of a human antibody AL-57, which binds to the alpha(L) I domain in a HA but not LA conformation. AL-57 was discovered by selection from a human Fab-displaying library using a locked-open HA I domain as target. AL-57 Fab-phage bound HA I domain-expressing K562 cells (HA cells) in a Mg(2+)-dependent manner. AL-57 IgG also bound HA cells and PBMCs, activated by Mg(2+)/EGTA, PMA, or DTT. The binding profile of AL-57 IgG on PBMCs was the same as that of ICAM-1, the main ligand of LFA-1. In contrast, an anti-alpha(L) murine mAb MHM24 did not distinguish between the HA and LA forms. Moreover, AL-57 IgG blocked ICAM-1 binding to HA cells with a potency greater than MHM24. It also inhibited ICAM-1 binding to PBMCs, blocked adhesion of HA cells to keratinocytes, and inhibited PHA-induced lymphocyte proliferation with potencies comparable with MHM24. These results indicate that specifically targeting the HA I domain is sufficient to inhibit LFA-1-mediated, adhesive functions. AL-57 represents a therapeutic candidate for treatment of inflammatory and autoimmune diseases.

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. Publishing Authors By Initials

L Huang,M Shimaoka,IJ Rondon,I Roy,Q Chang,M Po,DT Dransfield,RC Ladner,AS Edge,A Salas,CR Wood,TA Springer,EH Cohen,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: structure-activity relationship research

PUBMED ID PMID:

MEDLINE DATE:

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of leukocyte biology

VOLUME: 80

Page Numbers: 905-14

Journal Abbreviation: J. Leukoc. Biol.

ISSN: 0741-5400

DAY: 3

MONTH: 08

YEAR: 2006

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8405628

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. Keywords Mesh Terms:

KEYWORDS: Structure-Activity Relationship

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1. Information

Substance Name: Intercellular Adhesion Molecule-1

Registry Number: 126547-89-5

Grant and Affiliation Information for Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1.

AFFILIATION: Dyax Corporation, Cambridge, MA 02139, USA. lhuang@dyax.com

Country: United States

AGENCY: United States NCI

GRANT: R37 CA031798-26

ACRONYM: CA

MEDLINETA: J Leukoc Biol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1 Related Publications

• A polymorphism in New Zealand inbred mouse strains that inactivates phosphatidylcholine transfer protein.
• A standards-based approach for facilitating discovery of learning objects at the point of care.
• Atrial natriuretic peptide administered just prior to reperfusion limits infarction in rabbit hearts.
• Biomarkers in the diagnosis of Alzheimer's disease: are we ready?
• Cognitive predictors of functional decline in vascular dementia.
• Crohn's disease arthritis treated with infliximab: an open trial in four patients.
• Cryosurgery of the prostate: techniques and indications.
• Determination of ethylenediaminetetra-acetic acid in aqueous rinses of detergent-washed rubber stoppers of pharmaceutical vials using solid-phase extraction and capillary gas chromatography.
• Electrical activation of the human vestibulo-sympathetic reflex.
• Functional magnetic resonance imaging and magnetoencephalography differences associated with APOEepsilon4 in young healthy adults.
• Homozygous disruption of Pctp modulates atherosclerosis in apolipoprotein E-deficient mice.
• Identification and characterization of a human monoclonal antagonistic antibody AL-57 that preferentially binds the high-affinity form of lymphocyte function-associated antigen-1.
• Identification of a GABAA receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog.
• Impulsivity and the reinforcing value of cigarette smoking.
• Management of refractory ulcerative colitis.
• Mental health services for victims of disasters.
• Mental health services in primary care in 'developing' countries.
• Optimism, distress, health-related quality of life, and change in cancer antigen 125 among patients with ovarian cancer undergoing chemotherapy.
• Phosphorylation by DNA-dependent protein kinase is critical for apoptosis induction by insulin-like growth factor binding protein-3.
• Primary prevention in high-risk dyslipidemic patients without an established cardiovascular disease: Undertreatment and rationale for lipid-lowering therapy.
• Social role and birth cohort influences on gender-linked personality traits in women: a 20-year longitudinal analysis.
• TSA-induced cell death in prostate cancer cell lines is caspase-2 dependent and involves the PIDDosome.
• The cost-effectiveness of treating male trichomoniasis to avert HIV transmission in men seeking sexually transmitted disease care in Malawi.
• The physics of optimal decision making: a formal analysis of models of performance in two-alternative forced-choice tasks.
• The proximal convoluted tubule is a target for the uroguanylin-regulated natriuretic response.
• Treatment strategies for medulloblastoma and primitive neuroectodermal tumors.
• Writing about the benefits of an interpersonal transgression facilitates forgiveness.
• [Spatial orientation of the vestibulo-ocular reflex]
• [The effects of neuroleptics and social research in psychopharmacology.]
• p53, cellular proliferation, and apoptosis-related factors in thymic neuroendocrine tumors.