Rad23 as a reciprocal agent for stimulating or repressing immune responses

Helen A. Andersson, Marco F. Passeri, Michael A Barry

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The proteasome degrades cellular proteins and provides peptides for major histocompatibility complex (MHC) class I molecules to drive CD8 + T-cell responses to kill intracellular pathogens. Rad23 plays a role in protein degradation by targeting polyubiquitinated substrates to the proteasome via an N-terminal ubiquitin-like (UbL) domain that binds the proteasome and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitinated proteins. We demonstrate here that fusion of Rad23 or its UBA domain to the green fluorescent protein (GFP) targets this antigen to the proteasome for increased degradation in mammalian cells and enhanced antigen-specific CD 8+ T-cell responses in BALB/c mice. Conversely, we show that coexpression of unfused Rad23 with destabilized GFP inhibits degradation of the reporter protein and attenuates in vivo CD 8+ T-cell responses. Rad23 therefore holds promise as a useful agent either to enhance or attenuate cellular immune responses to suit the reciprocal immunologic needs of both gene therapy and genetic vaccine applications.

Original languageEnglish (US)
Pages (from-to)634-641
Number of pages8
JournalHuman Gene Therapy
Volume16
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

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Proteasome Endopeptidase Complex
Ubiquitin
Green Fluorescent Proteins
T-Lymphocytes
Proteolysis
Ubiquitin C
CD Antigens
Ubiquitinated Proteins
Protein Transport
Major Histocompatibility Complex
Cellular Immunity
Genetic Therapy
Proteins
Vaccines
Antigens
Peptides

ASJC Scopus subject areas

  • Genetics

Cite this

Rad23 as a reciprocal agent for stimulating or repressing immune responses. / Andersson, Helen A.; Passeri, Marco F.; Barry, Michael A.

In: Human Gene Therapy, Vol. 16, No. 5, 05.2005, p. 634-641.

Research output: Contribution to journalArticle

Andersson, Helen A. ; Passeri, Marco F. ; Barry, Michael A. / Rad23 as a reciprocal agent for stimulating or repressing immune responses. In: Human Gene Therapy. 2005 ; Vol. 16, No. 5. pp. 634-641.
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