Class II MHC/Peptide Interaction in Leishmania donovani Infection: Implications in Vaccine Design
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Class II MHC/Peptide Interaction in Leishmania donovani
Infection: Implications in Vaccine Design
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| Creator |
Roy, Koushik
Naskar, Kshudiram Ghosh, Moumita Roy, Syamal |
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| Subject |
Infectious Diseases and Immunology
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| Description |
We show that Leishmania donovani–infectedmacrophages (MFs) are capable of stimulatingMHC class II (MHC-II)–restricted T cells at 6 h of infection. At 48 h, infectedMFs (I-MFs) failed to stimulateMHC-II–restricted T cells but notMHC class I–restricted ones, in contrast to normalMFs. Such I-MFs could stimulate T cells at a higher Ag concentration, indicating that general Ag processing and trafficking of peptide–MHC-II complexes are not defective. Analysis of the kinetic parameters, like “kon” and “koff,” showed that
peptide–MHC-II complex formation is compromised in I-MFs comparedwith normal MFs. This indicates interference in loading of the cognate peptide to MHC-II, which may be due to the presence of a noncognate molecule. This notion received support from the finding that exposure of I-MFs to low pH or treatment with 2-(1-adamantyl)-ethanol, a molecule that favors peptide exchange, led to
T cell activation. When treated with 2-(1-adamantyl)-ethanol, splenocytes from 8 wk–infected BALB/c mice showed significantly higher antileishmanial T cell expansion in vitro compared with untreated controls. Hence, it is tempting to speculate that high, but not low, concentrations of cognate peptide may favor peptide exchange in I-MFs, leading to expansion of the antileishmanial T cell repertoire. The results suggest that a high Ag dose may overcome compromised T cell responses in visceral leishmaniasis, and this has an important implication in therapeutic vaccine design
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| Publisher |
American Association of Immunologists
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| Date |
2014
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2044/1/JOURNAL_OF_IMMUNOLOGY___192_(12__)__5873%2D5880;2014[01].pdf
Roy, Koushik and Naskar, Kshudiram and Ghosh, Moumita and Roy, Syamal (2014) Class II MHC/Peptide Interaction in Leishmania donovani Infection: Implications in Vaccine Design. The Journal of Immunology, 192 (12). pp. 5873-5880. ISSN 0022-1767 |
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| Relation |
http://dx.doi.org/10.4049/jimmunol.1302970
http://www.eprints.iicb.res.in/2044/ |
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