Universität zu Köln

Neerincx, Andreas, Jakobshagen, Kristin, Utermoehlen, Olaf, Buening, Hildegard, Steimle, Viktor and Kufer, Thomas A. (2014). The N-Terminal Domain of NLRC5 Confers Transcriptional Activity for MHC Class I and II Gene Expression. J. Immunol., 193 (6). S. 3090 - 3101. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 1550-6606

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Abstract

Ag presentation to CD4(+) and CD8(+) T cells depends on MHC class II and MHC class I molecules, respectively. One important regulatory factor of this process is the transcriptional regulation of MHC gene expression. It is well established that MHC class II transcription relies on the NLR protein CIITA. Recently, another NLR protein, NLRC5, was shown to drive MHC class I expression. The molecular mechanisms of the function of NLRC5 however remain largely elusive. In this study, we present a detailed functional study of the domains of NLRC5 revealing that the N-terminal domain of human NLRC5 has intrinsic transcriptional activity. Domain swapping experiments between NLRC5 and CIITA showed that this domain contributes to MHC class I and MHC class II gene expression with a bias for activation of MHC class I promoters. Delivery of this construct by adeno-associated viral vectors upregulated MHC class I and MHC class II expression in human cells and enhanced lysis of melanoma cells by CD8(+) cytotoxic T cells in vitro. Taken together, this work provides novel insight into the function of NLRC5 and CIITA in MHC gene regulation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neerincx, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Jakobshagen, Kristin UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Buening, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Steimle, Viktor UNSPECIFIED UNSPECIFIED UNSPECIFIED Kufer, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-430010
DOI:	10.4049/jimmunol.1401065
Journal or Publication Title:	J. Immunol.
Volume:	193
Number:	6
Page Range:	S. 3090 - 3101
Date:	2014
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	1550-6606
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BARE-LYMPHOCYTE-SYNDROME; NUCLEOTIDE-BINDING DOMAIN; LEUCINE-RICH REPEATS; FAMILY-MEMBER NLRC5; X-BOX REGION; COMPLEMENTATION CLONING; TRANSACTIVATOR CIITA; ANTIGEN PRESENTATION; DEPENDENT MANNER; KAPPA-B Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43001