title: Molecular and idiotypic analyses of the antibody response to Cryptococcus neoformans glucuronoxylomannan-protein conjugate vaccine in autoimmune and nonautoimmune mice.
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)F(1) (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 approximately C3H > C57BL/6 approximately NZB approximately NZW approximately 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 Vkappa5.1. 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.
authors.affiliation: Departments of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: G
authors.initials: G
authors.lastname: Nussbaum
authors.forename: S
authors.initials: S
authors.lastname: Anandasabapathy
authors.forename: J
authors.initials: J
authors.lastname: Mukherjee
authors.forename: M
authors.initials: M
authors.lastname: Fan
authors.forename: A
authors.initials: A
authors.lastname: Casadevall
authors.forename: M D
authors.initials: MD
authors.lastname: Scharff
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001483:Base Sequence; D003455:Cryptococcus neoformans / Q000276:immunology*; D018076:DNA, Complementary; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000276:immunology*; D011817:Rabbits; D013745:Tetanus Toxoid / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D005657:Fungal Vaccines; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D011134:Polysaccharides; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C027478:glucuronoxylomannan