Reduced cytokine-mediated up-regulation of HLA-DR in TAP-deficient fibroblasts

Jacques Zimmer*, Aurélie Poli, Emmanuel Andrès, Daniel Hanau, Nicolaas H.C. Brons, François Hentges

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Human deficiency in transporter associated with antigen processing (TAP) is characterized by a very low surface expression of human leukocyte antigen (HLA) class I molecules in hematopoietic and non hematopoietic cells. Among the latter, TAP-deficient skin fibroblasts have previously been shown by us to be very sensitive to lysis by activated autologous NK cells, even in the presence of cytokines that up-regulate HLA class I expression, a mechanism sufficient to protect normal fibroblasts from NK cell-mediated killing. Our complementary investigations on two TAP-deficient skin fibroblast cell lines surprisingly revealed that in response to proinflammatory cytokines, up-regulation of HLA-DR molecules at the cell surface is much less marked than in the case of normal skin fibroblasts. In contrast, the surface molecules CD40 and CD54 increase as much as observed on normal cells, suggesting that TAP-deficient fibroblasts are able to efficiently transduce cytokine-mediated stimulating signals. Transfection of an intact TAP gene into one of the TAP-deficient fibroblast cell lines restored a normal HLA class I expression that strongly increased upon IFN-γ-mediated stimulation, whereas HLA-DR still remained lower than in control cells. These results suggest that, in addition to the defect in the HLA class I antigen presentation pathway, HLA-DR up-regulation is affected in TAP-deficient skin fibroblasts through an unknown mechanism probably independent from TAP.

Original languageEnglish
Pages (from-to)109-118
Number of pages10
JournalImmunology Letters
Volume107
Issue number2
DOIs
Publication statusPublished - 15 Nov 2006

Keywords

  • Cytokines
  • Fibroblasts
  • HLA class II
  • TAP deficiency

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