The role of B/T costimulatory signals in the immunopotentiating activity of neisserial porin.
A T cell-dependent immune response to group C meningococcal capsular polysaccharide (CPS) can be elicited when CPS is conjugated to the class 3 neisserial porin (CPS-porin). Treatment of CPS-porin-immunized mice with B7-2 blocking monoclonal antibody (MAb) caused a dramatic reduction in the CPS-specific IgG response, treatment with anti-B7-1 MAb had no effect, and concurrent blockade of B7-1 and B7-2 resulted in a synergistic abrogation of the CPS-specific IgG response while the CPS IgM response was unaffected. Anti-CD40L MAb treatment caused a significant reduction of both CPS-specific IgG and IgM levels. In contrast, blockade of CTLA4 interactions resulted in increases in both CPS IgG and IgM responses in CPS-porin-immunized mice. These data support the hypothesis that the ability of neisserial porins to improve the immune response to poorly immunogenic antigens (e.g., polysaccharides) is related to porin-induced increases in B7-2 expression on antigen-presenting cells and enhanced B/T cell interactions.
Mackinnon
F G
FG
Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Ho
Y
Y
Blake
M S
MS
Michon
F
F
Chandraker
A
A
Sayegh
M H
MH
Wetzler
L M
LM
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D060908:CTLA-4 Antigen; D007115:Immunization Schedule; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D051379:Mice; D008809:Mice, Inbred C3H; D009344:Neisseria gonorrhoeae / Q000276:immunology; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D018272:Porins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001428:Bacterial Vaccines; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; D018272:Porins; C057699:porin protein, Neisseria; D000069594:Abatacept