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Infection and Immunity, May 2005, p. 2999-3006, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2999-3006.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

B-Cell and T-Cell Immune Responses to Experimental Helicobacter pylori Infection in Humans

Zhannat Z. Nurgalieva,1 Margaret E. Conner,2 Antone R. Opekun,1 Carl Q. Zheng,2 Susan N. Elliott,3 Peter B. Ernst,3,{dagger} Michael Osato,1 Mary K. Estes,2 and David Y. Graham1,2*

Department of Medicine,1 Department of Molecular Virology and Microbiology, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas,2 Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas3

Received 3 September 2004/ Returned for modification 13 October 2004/ Accepted 30 December 2004

The acute antibody and T-cell immune response to Helicobacter pylori infection in humans has not been studied systematically. Serum from H. pylori-naive volunteers challenged with H. pylori and cured after 4 or 12 weeks was tested by enzyme-linked immunosorbent assays for anti-H. pylori-specific immunoglobulin M (IgM) and IgA established using bacterial lysates from homologous (the infecting strain) and heterologous H. pylori. Proteins recognized by IgM antibody were identified by mass spectrometry of immunoreactive bands separated by two-dimensional gel electrophoresis. Mucosal T-cell subsets (CD4, CD8, CD3, and CD30 cells) were assessed by immunohistochemistry. All 18 infected volunteers developed H. pylori-specific IgM responses to both homologous or heterologous H. pylori antigens. H. pylori antigens reacted with IgM antibody at 4 weeks postinfection. IgM Western blotting showed immunoreactivity of postinfection serum samples to multiple H. pylori proteins with molecular weights ranging between 9,000 (9K) to 150K with homologous strains but only a 70K band using heterologous antigens. Two-dimensional electrophoresis demonstrated that production of H. pylori-specific IgM antibodies was elicited by H. pylori flagellins A and B, urease B, ABC transporter binding protein, heat shock protein 70 (DnaK), and alkyl hydroperoxide reductase. Mucosal CD3, CD4, and CD8 T-cell numbers increased following infection. IgM antibody responses were detected to a range of homologous H. pylori antigens 2 to 4 weeks postchallenge. The majority of H. pylori proteins were those involved in motility and colonization and may represent targets for vaccine development.

* Corresponding author. Mailing address: VAMC Rm. 3A-320 (111D), 2002 Holcombe Blvd., Houston, TX 77030. Phone: (713) 795-0332. Fax: (713) 790-1040. E-mail: dgraham{at}bcm.tmc.edu.

Editor: F. C. Fang

{dagger} Present address: Department of Medicine, University of Virginia, Charlottesville, Va.

Infection and Immunity, May 2005, p. 2999-3006, Vol. 73, No. 5
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.5.2999-3006.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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