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Class II MHC/Peptide Interaction in Leishmania donovani Infection: Implications in Vaccine Design

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Title Class II MHC/Peptide Interaction in Leishmania donovani
Infection: Implications in Vaccine Design
 
Creator Roy, Koushik
Naskar, Kshudiram
Ghosh, Moumita
Roy, Syamal
 
Subject Infectious Diseases and Immunology
 
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
 
Publisher American Association of Immunologists
 
Date 2014
 
Type Article
PeerReviewed
 
Format application/pdf
 
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
 
Relation http://dx.doi.org/10.4049/jimmunol.1302970
http://www.eprints.iicb.res.in/2044/