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Inhibition of T cel...
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Hermansson, AKarolinska Institutet
(author)
Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis
- Article/chapterEnglish2010
Publisher, publication year, extent ...
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2010-05-03
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Rockefeller University Press,2010
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:120404444
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http://kipublications.ki.se/Default.aspx?queryparsed=id:120404444URI
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https://doi.org/10.1084/jem.20092243DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Immune responses to oxidized low-density lipoprotein (oxLDL) are proposed to be important in atherosclerosis. To identify the mechanisms of recognition that govern T cell responses to LDL particles, we generated T cell hybridomas from human ApoB100 transgenic (huB100tg) mice that were immunized with human oxLDL. Surprisingly, none of the hybridomas responded to oxidized LDL, only to native LDL and the purified LDL apolipoprotein ApoB100. However, sera from immunized mice contained IgG antibodies to oxLDL, suggesting that T cell responses to native ApoB100 help B cells making antibodies to oxLDL. ApoB100 responding CD4+ T cell hybridomas were MHC class II–restricted and expressed a single T cell receptor (TCR) variable (V) β chain, TRBV31, with different Vα chains. Immunization of huB100tgxLdlr−/− mice with a TRBV31-derived peptide induced anti-TRBV31 antibodies that blocked T cell recognition of ApoB100. This treatment significantly reduced atherosclerosis by 65%, with a concomitant reduction of macrophage infiltration and MHC class II expression in lesions. In conclusion, CD4+ T cells recognize epitopes on native ApoB100 protein, this response is associated with a limited set of clonotypic TCRs, and blocking TCR-dependent antigen recognition by these T cells protects against atherosclerosis.
Added entries (persons, corporate bodies, meetings, titles ...)
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Ketelhuth, DFJKarolinska Institutet
(author)
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Strodthoff, D
(author)
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Wurm, M
(author)
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Hansson, EMKarolinska Institutet
(author)
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Nicoletti, A
(author)
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Paulsson-Berne, GKarolinska Institutet
(author)
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Hansson, GKKarolinska Institutet
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:The Journal of experimental medicine: Rockefeller University Press207:5, s. 1081-10931540-95380022-1007
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