Cognate stimulatory B-cell-T-cell interactions are critical for T-cell help recruited by glycoconjugate vaccines.
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.
Guttormsen
H K
HK
Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA. hilde-kari.guttormsen@channing.harvard.edu
Sharpe
A H
AH
Chandraker
A K
AK
Brigtsen
A K
AK
Sayegh
M H
MH
Kasper
D L
DL
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D001428:Bacterial Vaccines / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
D000907:Antibodies, Bacterial; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D001428:Bacterial Vaccines; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; D023201:CD40 Ligand