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J Virol 2007 Apr;81(7):3437-46

IgA is a natural ligand of the Hepatitis A virus cellular receptor 1, and their association enhances virus-receptor interactions.

Tami C, Silberstein E, Manangeeswaran M, Freeman GJ, Umetsu SE, Dekruyff RH, Umetsu DT, Kaplan GG

Kaplan GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA Northwestern Univ, Feinberg Sch Med, Dept Immunol Microbiol, Chicago, IL 60611 USA Harvard Univ, Childrens Hosp, Sch Med, Karp Labs,Div Immunol, Boston, MA 02115 USA


The Hepatitis A virus cellular receptor I (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 an HAVCR1/TIM1 Fc fusion protein. The transfected cells that bound to the human HAVCR1/TIM1 Fc contained cDNA of human immunoglobulin alpha-1 heavy (Igalpha1) and lambda light (Iglambda) chain, and secreted human IgA1lambda antibody that bound to the cell surface. Cotransfection of the isolated Igalpha1 and Iglambda cDNAs to naive dog cells resulted in the secretion of IgA1lambda that bound to HAVCR1/TIM1 Fc but not to a poliovirus receptor Fc fusion protein in a capture ELISA. The interaction of HAVCR1/TIM1with IgA was inhibited with monoclonal antibodies (mAb) against Igalpha1 and Iglambda, excess IgA1lambda, 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 the HAVCR1/TIM1. IgA enhanced significantly the neutralization of HAV by HAVCR1/TIM1 Fc. Our results indicate that IgA1lambda is a specific ligand of HAVCR1/TIM1 and that their association has a synergistic effect in virus-receptor interactions.

Category: Journal Article
PubMed ID: #17229699
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29