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

The antibody response to Cryptococcus neoformans capsular glucuronoxylomann an (GXM) in BALB/c mice frequently expresses the 2H1 idiotype (Id) and is r estricted in variable gene usage. This study examined the immunogenicity of GXM-protein conjugates, V (variable)-region usage, and 2H1 Id expression i n seven mouse strains: BALB/c, C57BL/6, A/J, C3H, NZB, NZW, and (NZB x NZW) F-1 (NZB/W), Ail mouse strains responded to vaccination with GXM conjugated to tetanus toroid (TI), the relative magnitude of the antibody response be ing BALB/c similar to C3H > C57BL/6 similar to NZB similar to NZW similar t o NZB/W > A/J. Analysis of serum antibody responses to GXM with polyclonal and monoclonal antibodies to the 2H1 Id revealed significant inter- and int rastrain 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(+)) a nd structurally similar to those previously generated in BALB/c mice, inclu ding the usage of a V-H from the 7183 family and V kappa 5.1. Administratio n of both 2H1 Id(+) and Id(-) MAbs from NZB/W and C3H/H3 mice prolonged sur vival 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 primar y and secondary responses of several mouse strains; and (ii) that there is conservation of V-region usage and length of the third complementarity-dete rmining region in antibodies from three mouse strains. The results suggest that V-region restriction is a result of antibody structural requirements n ecessary for binding an immunodominant antigen in GXM.