Cholesterol lowering drug may infl uence cellular immune response by altering MHC II function
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Cholesterol lowering drug may infl uence cellular immune
response by altering MHC II function
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| Creator |
Roy, Koushik
Ghosh, Moumita Pal, Tuhin Kumar Chakrabarti, Saikat Roy, Syamal |
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| Subject |
Infectious Diseases and Immunology
Structural Biology & Bioinformatics |
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| Description |
Major histocompatibility complex class II (MHC II)
expressed on the surface of antigen-presenting cells (APCs)
displays peptides to CD4 + T cells. Depletion of membrane
cholesterol from APCs by methyl � -cyclodextrin treatment
compromises peptide-MHC II complex formation coupled
with impaired binding of conformational antibody, which
binds close to the peptide binding groove of MHC II. Interestingly,the total cell surface of MHC II remains unaltered.These defects can be corrected by restoring membrane cholesterol.In silico docking studies with a three-dimensional model showed the presence of a cholesterol binding site in the transmembrane domain of MHC II (TM-MHC - II). From the binding studies it was clear that cholesterol, indeed, interacts with the TM-MHC - II and alters its conformation. Mutation of cholesterol binding residues (F240, L243, and
F246) in the TM-MHC - II decreased the affi nity for cholesterol.
Furthermore, transfection of CHO cells with full-length
mutant MHC II, but not wild-type MHC II, failed to activate
antigen-specifi c T cells coupled with decreased binding of conformation-
specifi c antibodies. Thus, cholesterol-induced
conformational change of TM-MHC - II may allosterically
modulate the peptide binding groove of MHC II leading to
T cell activation. —Roy, K., M. Ghosh, T. K. Pal, S. Chakrabarti,
and S. Roy. Cholesterol lowering drug may infl uence cellular
immune response by altering MHC II
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| Publisher |
American Society for Biochemistry and Molecular Biology
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| Date |
2013
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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/2408/1/Journal_of_Lipid_Research_Volume_54%2C_2013.pdf
Roy, Koushik and Ghosh, Moumita and Pal, Tuhin Kumar and Chakrabarti, Saikat and Roy, Syamal (2013) Cholesterol lowering drug may infl uence cellular immune response by altering MHC II function. Journal of Lipid Research, 54. pp. 3016-3115. |
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| Relation |
http://dx.doi.org/10.1194/jlr.M041954
http://www.eprints.iicb.res.in/2408/ |
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