NDLI: Class II MHC/peptide interaction in Leishmania donovani infection: implications in vaccine design.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Roy, Syamal Ghosh, Moumita Naskar, Kshudiram Roy, Koushik
Description	Country affiliation: India Author Affiliation: Roy K ( Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.); Naskar K ( Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.); Ghosh M ( Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.); Roy S ( Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India sroy@iicb.res.in.)
Abstract	We show that Leishmania donovani-infected macrophages (MΦs) are capable of stimulating MHC class II (MHC-II)-restricted T cells at 6 h of infection. At 48 h, infected MΦs (I-MΦs) failed to stimulate MHC-II-restricted T cells but not MHC class I-restricted ones, in contrast to normal MΦs. Such I-MΦs 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-MΦs compared with normal MΦs. 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-MΦs 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-MΦs, 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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Protozoan Immunology Histocompatibility Antigens Class Ii Leishmania Donovani Leishmaniasis Vaccines Leishmaniasis, Visceral Macrophages Peptides Protozoan Proteins Metabolism Animals Lymphocyte Activation Parasitology Pathology Mice Mice, Inbred Balb C T-lymphocytes Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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