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Infection and Immunity, December 1999, p. 6375-6384, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Cognate Stimulatory B-Cell-T-Cell Interactions Are Critical for T-Cell Help Recruited by Glycoconjugate Vaccines

Hilde-Kari Guttormsen,1,* Arlene H. Sharpe,2 Anil K. Chandraker,3 Anne Karin Brigtsen,1,dagger Mohammed H. Sayegh,3 and Dennis L. Kasper1,4

Channing Laboratory, Department of Medicine,1 Immunology Research Division, Department of Pathology,2 and Laboratory of Immunogenetics and Transplantation, Department of Medicine,3 Brigham and Women's Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School,4 Boston, Massachusetts 02115

Received 7 April 1999/Returned for modification 15 June 1999/Accepted 7 September 1999

Covalent linkage of a bacterial polysaccharide to an immunogenic protein greatly enhances the carbohydrate's immunogenicity and induces polysaccharide-specific B-cell memory in vivo. These findings have spurred the development of glycoconjugate vaccines for serious bacterial infections. The specific B-cell-T-cell interactions responsible for recruitment of T-cell help by glycoconjugate vaccines are not well defined. We used mice deficient in molecules critical for stimulatory, cognate B-cell-T-cell interactions to study how T cells improve the immunogenicity of a glycoconjugate vaccine against group B streptococcal disease. Isotype switching to immunoglobulin G (IgG) was abrogated in mice deficient in major histocompatibility complex (MHC) class II antigen (Ag)-T-cell receptor (TCR), B7-CD28, or CD40-CD40L interactions. However, expression of either the B7-1 or the B7-2 molecule on antigen-presenting cells was sufficient for optimal T-cell costimulation. T cells activated by the vaccine also played a pivotal role in determining the magnitude of the IgM response to the polysaccharide. Comparable results were obtained with pathway antagonists. These data suggest that MHC class II Ag-TCR, B7-CD28, and CD40-CD40L interactions are critical for immune responses to glycoconjugate vaccines in vivo.

* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Ave., Boston, MA 02115. Phone: (617) 525-2192. Fax: (617) 731-1541. E-mail: hilde-kari.guttormsen{at}channing.harvard.edu.

dagger Present address: Department of Pediatrics, Ullevål Hospital, University of Oslo, Oslo, Norway.

Infection and Immunity, December 1999, p. 6375-6384, Vol. 67, No. 12
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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