T cell proliferative responses to malondialdehyde-acetaldehyde haptenated protein are scavenger receptor mediated

Monte S. Willis, Geoffrey M. Thiele, Dean J. Tuma, Lynell W. Klassen

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with ∼32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.

Original languageEnglish (US)
Pages (from-to)1381-1399
Number of pages19
JournalInternational Immunopharmacology
Volume3
Issue number10-11
DOIs
StatePublished - Oct 2003
Externally publishedYes

Keywords

  • Antigen processing and presentation
  • Malondialdehyde-acetaldehyde (MAA)
  • Scavenger receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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