Induction of phosphocholine-specific antibodies in X-linked immune deficient mice: in vivo protection against a Streptococcus pneumoniae challenge. 1994

J J Kenny, and G Guelde, and R T Fischer, and D L Longo
Biological Carcinogenesis Development Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.

X-linked immune deficient (XID) mice are susceptible to infection with Streptococcus pneumoniae because they fail to mount an immune response to the immunodominant phosphocholine (PC) epitope on the bacterial cell wall. It is difficult to induce PC-specific antibodies in XID mice because PC-specific B cells expressing the T15-, M167- and M603 idiotype (Id), which provide protection against S. pneumoniae, are deleted in these mice via an antigen-specific, receptor-mediated process. In addition, the standard PC hapten, p-diazophenylphosphocholine (DPPC), induces high affinity phenylphosphocholine (PPC)-specific antibodies in XID mice, which are not protective against S. pneumoniae. We have used a novel PC hapten, p-nitrophenyl-6-(O-phosphocholine)hydroxyhexanoate (EPC), to induce PC-specific antibodies in XID mice. The immune response to EPC-keyhole limpet hemacyanin (KLH) is dominated by IgG1, VH1+, T15-Id-, PC-inhibitable antibodies. A small IgM anti-PC response having a consistent T15-Id+ component is also induced in XID mice, whereas normal mice produce a large IgM response dominated by T15-Id+ antibodies. The immune response to EPC-KLH remains predominantly PC-inhibitable even after multiple immunizations, while the response to DPPC-KLH becomes dominated by PPC-specific antibodies. C.CBA/N mice immunized twice with EPC-KLH are protected against 10(4) S. pneumoniae while as few as 10 bacteria are 100% lethal for the unimmunized controls. The ability of EPC-protein to induce a long-lived, PC-specific response should make this hapten a potential TD vaccine candidate for S. pneumoniae.

UI MeSH Term Description Entries
D007153 Immunologic Deficiency Syndromes Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral. Antibody Deficiency Syndrome,Deficiency Syndrome, Immunologic,Deficiency Syndromes, Antibody,Deficiency Syndromes, Immunologic,Immunologic Deficiency Syndrome,Immunological Deficiency Syndromes,Antibody Deficiency Syndromes,Deficiency Syndrome, Antibody,Deficiency Syndrome, Immunological,Deficiency Syndromes, Immunological,Immunological Deficiency Syndrome,Syndrome, Antibody Deficiency,Syndrome, Immunologic Deficiency,Syndrome, Immunological Deficiency,Syndromes, Antibody Deficiency,Syndromes, Immunologic Deficiency,Syndromes, Immunological Deficiency
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D010767 Phosphorylcholine Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction. Choline Chloride Dihydrogen Phosphate,Choline Phosphate Chloride,Phosphorylcholine Chloride,Choline Phosphate,Phosphocholine,Chloride, Choline Phosphate,Chloride, Phosphorylcholine,Phosphate Chloride, Choline,Phosphate, Choline
D002208 Caproates Derivatives of caproic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a carboxy terminated six carbon aliphatic structure. Hexanoates,Caproic Acid Derivatives,Caproic Acids,Hexanoic Acid Derivatives,Hexanoic Acids,Acid Derivatives, Caproic,Acid Derivatives, Hexanoic,Acids, Caproic,Acids, Hexanoic,Derivatives, Caproic Acid,Derivatives, Hexanoic Acid
D005260 Female Females
D006241 Haptens Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. Hapten,Contact-Sensitizing Agents,Agents, Contact-Sensitizing,Contact Sensitizing Agents
D006433 Hemocyanins Metalloproteins that function as oxygen transport proteins in the HEMOLYMPH of MOLLUSKS and ARTHROPODS. They are characterized by two copper atoms, coordinated with HISTIDINE residues, that reversibly bind a single oxygen molecule; they do not contain HEME groups. Hemocyanin,alpha-Haemocyanin,alpha-Hemocyanin,alpha-Hemocyanins,alpha Haemocyanin,alpha Hemocyanin,alpha Hemocyanins

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