In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 11 ( 2000-05-23), p. 6031-6036
Abstract:
Phosphocholine (PC) is the immunodominant epitope found on the surface of Streptococcus pneumoniae ( SPn ). T15-idiotype Abs, whose heavy (H) chain variable region is encoded by the V1 gene, are dominant in the anti-PC response in adult mice and protect mice from lethal pneumococcal infection. The ability of anti-PC Abs using H chains other than the V1 H chain to protect against pneumococcal infection remains controversial. We generated V1 −/− knockout mice to determine whether protective anti-PC Abs could be produced in the absence of the V1 gene. No anti-PC Abs were produced in V1 −/− mice immunized with avirulent SPn ; however, PC-BSA binding Abs were induced after immunization with PC-keyhole limpet hemocyanin but at significantly lower levels than those in wild-type mice. These Abs provided poor protection against virulent SPn ; thus, 〈 25% of V1 −/− mice survived challenge with 10 4 bacteria as compared with 100% survival of V1 +/+ mice. The anti-PC Abs in V1 −/− mice were heteroclitic, binding to nitrophenyl-PC better than to PC. None of nine hybridomas produced from V1 −/− mice provided passive protection. However, the V1 −/− mice produced normal amounts of Ab to SPn proteins that can partially protect mice against SPn . These data indicate that the V1 gene is critical for the production of anti-PC Abs providing optimum protection against infection with SPn , and the V1 −/− mice could be useful in unmasking epitopes other than the immunodominant PC epitope on SPn capable of providing cross protection.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.110039497
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2000
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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