Molecular and idiotypic analyses of the antibody response to Cryptococcus neoformans glucuronoxylomannan-protein conjugate vaccine in autoimmune and nonautoimmune mice

Gabriel Nussbaum, Sharmila Anandasabapathy, Jean Mukherjee, Manxia Fan, Arturo Casadevall, Matthew D. Scharff

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The antibody response to Cryptococcus neoformans capsular glucuronoxylomannan (GXM) in BALB/c mice frequently expresses the 2H1 idiotype (Id) and is restricted in variable gene usage. This study examined the immunogenicity of GXM-protein conjugates, V (variable)-region usage, and 2H1 Id expression in seven mouse strains: BALB/c, C57BL/6, A/J, C3H, NZB, NZW, and (NZB x NZW)F1 (NZB/W). All mouse strains responded to vaccination with GXM conjugated to tetanus toxoid (TT), the relative magnitude of the antibody response being BALB/c ~ C3H > C57BL/6 ~ NZB ~ NZW ~ NZB/W > A/J. Analysis of serum antibody responses to GXM with polyclonal and monoclonal antibodies to the 2H1 Id revealed significant inter- and intrastrain differences in idiotype expression. Thirteen monoclonal antibodies (MAbs) (two immunoglobulin M [IgM], three IgG3, one IgG1, three IgG2a, two IgG2b, and two IgA) to GXM were generated from one NZB/W mouse and one C3H/He mouse. The MAbs from the NZB/W mouse were all 2H1 Id positive (Id+) and structurally similar to those previously generated in BALB/c mice, including the usage of a V(H) from the 7183 family and Vκ5.1. Administration of both 2H1 Id+ and Id- MAbs from NZB/W and C3H/H3 mice prolonged survival in a mouse model of cryptococcosis. Our results demonstrate (i) that V-region restriction as indicated by the 2H1 Id is a feature of both primary and secondary responses of several mouse strains; and (ii) that there is conservation of V-region usage and length of the third complementarity- determining region in antibodies from three mouse strains. The results suggest that V-region restriction is a result of antibody structural requirements necessary for binding an immunodominant antigen in GXM.

Original languageEnglish (US)
Pages (from-to)4469-4476
Number of pages8
JournalInfection and Immunity
Volume67
Issue number9
StatePublished - 1999

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Conjugate Vaccines
Cryptococcus neoformans
Antibody Formation
Monoclonal Antibodies
Inbred NZB Mouse
Proteins
Inbred C3H Mouse
Immunoglobulin G
Complementarity Determining Regions
Cryptococcosis
Immunodominant Epitopes
Tetanus Toxoid
Antibodies
glucuronoxylomannan
Immunoglobulin A
Immunoglobulin M
Vaccination
Serum
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Molecular and idiotypic analyses of the antibody response to Cryptococcus neoformans glucuronoxylomannan-protein conjugate vaccine in autoimmune and nonautoimmune mice. / Nussbaum, Gabriel; Anandasabapathy, Sharmila; Mukherjee, Jean; Fan, Manxia; Casadevall, Arturo; Scharff, Matthew D.

In: Infection and Immunity, Vol. 67, No. 9, 1999, p. 4469-4476.

Research output: Contribution to journalArticle

Nussbaum, Gabriel ; Anandasabapathy, Sharmila ; Mukherjee, Jean ; Fan, Manxia ; Casadevall, Arturo ; Scharff, Matthew D. / Molecular and idiotypic analyses of the antibody response to Cryptococcus neoformans glucuronoxylomannan-protein conjugate vaccine in autoimmune and nonautoimmune mice. In: Infection and Immunity. 1999 ; Vol. 67, No. 9. pp. 4469-4476.
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abstract = "The antibody response to Cryptococcus neoformans capsular glucuronoxylomannan (GXM) in BALB/c mice frequently expresses the 2H1 idiotype (Id) and is restricted in variable gene usage. This study examined the immunogenicity of GXM-protein conjugates, V (variable)-region usage, and 2H1 Id expression in seven mouse strains: BALB/c, C57BL/6, A/J, C3H, NZB, NZW, and (NZB x NZW)F1 (NZB/W). All mouse strains responded to vaccination with GXM conjugated to tetanus toxoid (TT), the relative magnitude of the antibody response being BALB/c ~ C3H > C57BL/6 ~ NZB ~ NZW ~ NZB/W > A/J. Analysis of serum antibody responses to GXM with polyclonal and monoclonal antibodies to the 2H1 Id revealed significant inter- and intrastrain differences in idiotype expression. Thirteen monoclonal antibodies (MAbs) (two immunoglobulin M [IgM], three IgG3, one IgG1, three IgG2a, two IgG2b, and two IgA) to GXM were generated from one NZB/W mouse and one C3H/He mouse. The MAbs from the NZB/W mouse were all 2H1 Id positive (Id+) and structurally similar to those previously generated in BALB/c mice, including the usage of a V(H) from the 7183 family and Vκ5.1. Administration of both 2H1 Id+ and Id- MAbs from NZB/W and C3H/H3 mice prolonged survival in a mouse model of cryptococcosis. Our results demonstrate (i) that V-region restriction as indicated by the 2H1 Id is a feature of both primary and secondary responses of several mouse strains; and (ii) that there is conservation of V-region usage and length of the third complementarity- determining region in antibodies from three mouse strains. The results suggest that V-region restriction is a result of antibody structural requirements necessary for binding an immunodominant antigen in GXM.",
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AU - Casadevall, Arturo

AU - Scharff, Matthew D.

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