Isolation, expression, and the primary structure of HLA-Cw1 and HLA-Cw2 genes: evolutionary aspects

Güssow, Detlef; Rein, Rita S.; Meijer, Ingeborg; Hoog, Wout de; Seemann, G.; Hochstenbach, Frans M.; Ploegh, Hidde L.

doi:10.1007/bf00351094

Cited by 31 publications

(40 citation statements)

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“…Since the strongest in vivo protection was detected in site a, we wished to determine whether site a binding activity is also absent in brain nuclear extracts. The site a core is highly conserved among MHC class I genes of various species (murine H-2K' [3], Kd [44], Ld [40], Dd [42], and D' [76]; human HLAB-27 [79], BW57 [31], CW1 and CW2 [27], and CW5 [74]; and swine SLAPD1 [17]). An electrophoretic mobility shift assay was performed with nuclear extracts prepared from mouse brain and spleen and 32P-labeled oligonucleotides corresponding to site a of the H-2K" gene (-87 to -117) as a probe.…”

Section: Resultsmentioning

confidence: 99%

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

et al. 1992

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The major histocompatibility complex (MHC) class I HLA-B7 transgene carrying a 660-bp upstream sequence is expressed in the mouse with tissue specificity that parallels that of the expression of endogenous mouse MHC class I (H-2) genes. We have performed in vivo genomic footprinting for the HLA-B7 transgene and the endogenous HN2Kb gene. We show that the upstream region of both the transgene and the endogenous gene was extensively occupied in spleen tissue, where these genes are expressed at high levels. In contrast, no occupancy was detected in brain tissue, where expression of these genes is virtually absent. Sites exhibiting in vivo protection correspond to cis elements previously shown to bind to nuclear factors in vitro, including the constitutive enhancer region I and the interferon response element. The strongest tissue-specific protection was detected at site a, located downstream from the interferon response element. Site of bound a constitutively expressed nuclear factor(s) in vitro that exhibited an overlapping specificity which may involve a nuclear hormone receptor, RXR, and an AP-1-related factor. Site a was functional in vivo, as it enhanced MHC class I transcription in lymphocytes. These results show that the tissue-specific occupancy of the MHC class I regulatory sequences in vivo correlates with their expression and suggest that in vivo occupancy is controlled by a mechanism other than the mere presence of factors capable of binding to these sites. Our results suggest that a sequence present in the 660-bp upstream region in a human leukocyte antigen gene directs tissue-specific occupancy of MHC class I genes in vivo, independently of their position and copy number, illustrating a potential advantage of using a transgene for delimitation of the sequence requirement for in vivo occupancy.

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Section: Resultsmentioning

confidence: 99%

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

et al. 1992

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“…In contrast, HIV Nef and KHSV K5 focus on the class I transmembrane and tail regions for distinguishing between class I locus products (5,15). These segments contain an abundance of locus-specific residues (11). Most of the polymorphic residues in class I are concentrated in regions that contact peptide or TCR, and US2 does not compete with TCR for class I association.…”

Section: Discussionmentioning

confidence: 99%

Human Cytomegalovirus US2 Endoplasmic Reticulum-Lumenal Domain Dictates Association with Major Histocompatibility Complex Class I in a Locus-Specific Manner

Gewurz¹,

Wang²,

Tortorella³

et al. 2001

J Virol

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The human cytomegalovirus-encoded US2 glycoprotein targets endoplasmic reticulum-resident major histocompatibility complex (MHC) class I heavy chains for rapid degradation by the proteasome. We demonstrate that the endoplasmic reticulum-lumenal domain of US2 allows tight interaction with class I molecules encoded by the HLA-A locus. Recombinant soluble US2 binds properly folded, peptide-containing recombinant HLA-A2 molecules in a peptide sequence-independent manner, consistent with US2's ability to broadly downregulate class I molecules. The physicochemical properties of the US2/MHC class I complex suggest a 1:1 stoichiometry. These results demonstrate that US2 does not require additional cellular proteins to specifically interact with soluble class I molecules. Binding of US2 does not significantly alter the conformation of class I molecules, as a soluble T-cell receptor can simultaneously recognize class I molecules associated with US2. The lumenal domain of US2 can differentiate between the products of distinct class I loci, as US2 binds several HLA-A locus products while being unable to bind recombinant HLA-B7, HLA-B27, HLA-Cw4, or HLA-E. We did not observe interaction between soluble US2 and either recombinant HLA-DR1 or recombinant HLA-DM. The substrate specificity of US2 may help explain the presence in human cytomegalovirus of multiple strategies for downregulation of MHC class I molecules.

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“…In addition, the Ϫ35 SNP has recently been associated with levels of HLA-C expression and may indicate a new role for HLA-C alleles in HIV-1 control (40). One reason that has been postulated to explain the lack of HLA-C association with immune pressure is the lower expression of HLA-C on the cell surface (18,36,37). However, HLA-C, unlike HLA-A and HLA-B, is not downregulated by the Nef protein, and this factor, therefore, may explain the lower expression level (9).…”

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confidence: 99%

HLA-Cw*03-Restricted CD8⁺T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation

Honeyborne

Codoñer

Leslie

et al. 2010

J Virol

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Isolation, expression, and the primary structure of HLA-Cw1 and HLA-Cw2 genes: evolutionary aspects

Cited by 31 publications

References 0 publications

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

Human Cytomegalovirus US2 Endoplasmic Reticulum-Lumenal Domain Dictates Association with Major Histocompatibility Complex Class I in a Locus-Specific Manner

HLA-Cw*03-Restricted CD8⁺T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation

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Isolation, expression, and the primary structure of HLA-Cw1 and HLA-Cw2 genes: evolutionary aspects

Cited by 31 publications

References 0 publications

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

Occupancy of upstream regulatory sites in vivo coincides with major histocompatibility complex class I gene expression in mouse tissues.

Human Cytomegalovirus US2 Endoplasmic Reticulum-Lumenal Domain Dictates Association with Major Histocompatibility Complex Class I in a Locus-Specific Manner

HLA-Cw*03-Restricted CD8+T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation

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HLA-Cw*03-Restricted CD8⁺T-Cell Responses Targeting the HIV-1 Gag Major Homology Region Drive Virus Immune Escape and Fitness Constraints Compensated for by Intracodon Variation