Identification of gingipain-specific I-A(b) -restricted CD4+ T cells following mucosal colonization with Porphyromonas gingivalis in C57BL/6 mice.

Identification of gingipain-specific I-A(b) -restricted CD4+ T cells following mucosal colonization with Porphyromonas gingivalis in C57BL/6 mice.
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DOI:
10.1111/omi.12038
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发表时间:
2013-12
影响因子:
3.7
通讯作者:
Costalonga M
Costalonga M
中科院分区:
医学3区
文献类型:
--
作者:
Bittner-Eddy PD;Fischer LA;Costalonga M

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Chronic periodontitis is associated with Porphyromonas gingivalis infection. Although virulence factors of P. gingivalis are hypothesized to contribute to the pathogenesis of periodontitis, it is unclear whether the local CD4+ T-cell-mediated response they elicit prevents or contributes to periodontal bone destruction. We hypothesize that major histocompatibility complex class II I-Ab-binding peptides existing in Kgp and RgpA are presented to CD4+ T cells during P. gingivalis oral colonization. The protein sequences of gingipains RgpA and Kgp, and OMP40 and OMP41 of P. gingivalis were scanned using an I-Ab-binding matrix. From this analysis we identified 53 candidate peptides that had the potential to engage the peptide-binding groove of the I-Ab molecule of C57BL/6 mice. An ELISpot-based screen revealed those peptide-primed effector/memory CD4+ T cells that could be re-stimulated in vitro with P. gingivalis or the peptide itself to produce interleukin-17A or interferon-γ. Two immunodominant peptides, Kgp467–477 (pKgp) and RgpA1054–1064/Kgp1074–1084 (pR/Kgp) were identified and engineered to be displayed on I-Ab molecular tetramers. Peptide pR/Kgp is conserved across all sequenced P. gingivalis strains. C57BL/6 mice were orally inoculated with P. gingivalis strain 53977 and cervical lymph node cells were stained with phycoerythrin-conjugated pKgp::I-Ab and pR/Kgp::I-Ab tetramers. We found that only pR/Kgp::I-Ab bound with the desired specificity to gingipain-specific CD4+ T cells. The pR/Kgp::I-Ab tetramer complex will allow the identification of effector/memory CD4+ T cells specific for two virulence factors of P. gingivalis strains associated with periodontal disease.
DOI: 10.1128/iai.67.6.2804-2809.1999
发表时间: 1999-06-01
影响因子: 3.1
作者:
Baker, PJ;Dixon, M;Roopenian, DC
通讯作者: Roopenian, DC
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