Immunoglobulin A (IgA) Is a Natural Ligand of Hepatitis A Virus Cellular Receptor 1 (HAVCR1), and the Association of IgA with HAVCR1 Enhances Virus-Receptor Interactions
- 1 April 2007
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (7), 3437-3446
- https://doi.org/10.1128/jvi.01585-06
Abstract
The hepatitis A virus cellular receptor 1 (HAVCR1/TIM1), a member of the T-cell immunoglobulin mucin (TIM) family, is an important atopy susceptibility gene in humans. The exact natural function of HAVCR1/TIM1 and the inverse association between HAV infection and prevention of atopy are not well understood. To identify natural ligands of human HAVCR1/TIM1, we used an expression cloning strategy based on the binding of dog cells transfected with a human lymph node cDNA library to a HAVCR1/TIM1 Fc fusion protein. The transfected cells that bound to the human HAVCR1/TIM1 Fc contained cDNA of human immunoglobulin alpha 1 heavy (Igα1) and lambda light (Igλ) chain and secreted human IgA1λ antibody that bound to the cell surface. Cotransfection of the isolated Igα1 and Igλ cDNAs to naïve dog cells resulted in the secretion of IgA1λ that bound to HAVCR1/TIM1 Fc but not to a poliovirus receptor Fc fusion protein in a capture enzyme-linked immunosorbent assay. The interaction of HAVCR1/TIM1 with IgA was inhibited by monoclonal antibodies (MAbs) against Igα1 and Igλ, excess IgA1λ, or anti-HAVCR1/TIM1 MAb. IgA did not inhibit HAV infection of African green monkey cells, suggesting that the IgA and the virus binding sites are in different epitopes on HAVCR1/TIM1. IgA enhanced significantly the neutralization of HAV by HAVCR1/TIM1 Fc. Our results indicate that IgA1λ is a specific ligand of HAVCR1/TIM1 and that their association has a synergistic effect in virus-receptor interactions.Keywords
This publication has 53 references indexed in Scilit:
- The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunityNature Immunology, 2005
- IgA-coated particles of Hepatitis A virus are translocalized antivectorially from the apical to the basolateral site of polarized epithelial cells via the polymeric immunoglobulin receptorJournal of General Virology, 2005
- Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell immunoglobulin mucin 3 gene are associated with asthma in an African American populationJournal of Allergy and Clinical Immunology, 2005
- Mucosal Immunity in Asthma and Chronic Obstructive Pulmonary Disease: A Role for Immunoglobulin A?Proceedings of the American Thoracic Society, 2004
- Hepatitis A virus link to atopic diseaseNature, 2003
- Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune diseaseNature, 2002
- Neutralization of Hepatitis A Virus (HAV) by an Immunoadhesin Containing the Cysteine-Rich Region of HAV Cellular Receptor-1Journal of Virology, 2001
- Atypical clinical manifestations of hepatitis AVaccine, 1992
- CD4/Immunoglobulin Interaction: Implications for Immune Physiology and AutoimmunityInternational Reviews of Immunology, 1991
- Selective extraction of polyoma DNA from infected mouse cell culturesJournal of Molecular Biology, 1967