From transcription to cell surface expression, the induction of MHC class II I-Aα by interferon-γ in macrophages is regulated at different levels

2001 ◽  
Vol 53 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Martin Cullell-Young ◽  
Marta Barrachina ◽  
Carlos López-López ◽  
Eduard Goñalons ◽  
Jorge Lloberas ◽  
...  
1993 ◽  
Vol 178 (2) ◽  
pp. 731-735
Author(s):  
R R Olson ◽  
J J Reuter ◽  
K Scalf

Recombinant major histocompatibility complex (MHC) class II molecules were expressed with extracellular polypeptide domains reorganized to form heavy (H) and light (L) chains (alpha 1-beta 1-beta 2 and alpha 2) analogous to class I. Accurate protein folding and dimerization is demonstrated by the ability of this 3+1-DR1 construct to bind class II-restricted peptides and stimulate CD4+ T cells. Cell surface expression of a functional class II molecule consisting of H and L chains supports the validity of current class II models and affirms the evolutionary relatedness of class I/II. MHC functions that differ between class I/II may be influenced by domain configuration, and the use of domain-shifted constructs will allow examination of this possibility.


1988 ◽  
Vol 168 (3) ◽  
pp. 823-837 ◽  
Author(s):  
J M Buerstedde ◽  
L R Pease ◽  
A E Nilson ◽  
M P Bell ◽  
C Chase ◽  
...  

A panel of mutant class II genes have been constructed using site-directed mutagenesis and DNA-mediated gene transfer. Using this technique, Ak beta polypeptides have been altered by substituting one or more Ad beta-specific residues at polymorphic positions in the beta 1 domain. Transfection of M12.C3 B lymphoma cells with most mutant Ak beta* genes results in the expression of Ak beta* Ad alpha molecules on the cell surface. However, the substitution of a single d allele residue at position 78 or 86 in the Ak beta polypeptide results in either the complete absence or very low levels, respectively, of cell surface expression of the Ak beta* Ad alpha molecule, but does not alter Ak beta* Ak alpha expression. The T.86 Ak beta* Ad alpha is expressed primarily in an intracellular compartment while the T.78 Ak beta* molecule does not appear to be produced. The core-glycosylated T.78 Ak beta* polypeptide does, however, form a complex intracellularly with the core-glycosylated Ii polypeptide. Substitution of the combination of d allele residues at Ak beta polymorphic positions 9, 12, 13, 14, and 17 results in the absence of Ak beta* Ak alpha cell surface expression but does not alter the expression of this mutant Ak beta* polypeptide with the Ad alpha polypeptide. These allele-specific expression mutants demonstrate that substitution at certain beta 1 domain positions may result in the alteration of Ia cell surface expression and that the transport of Ia molecules from the Golgi apparatus to the cell surface may be regulated by signals that are determined by the interaction of polymorphic residues in both the alpha and beta polypeptides.


Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  

Abstract The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.


Virology ◽  
2007 ◽  
Vol 359 (1) ◽  
pp. 212-219 ◽  
Author(s):  
Masahiro Niikura ◽  
Taejoong Kim ◽  
Henry D. Hunt ◽  
Joan Burnside ◽  
Robin W. Morgan ◽  
...  

2011 ◽  
Vol 286 (44) ◽  
pp. 37964-37975 ◽  
Author(s):  
Claire Germain ◽  
Anders Meier ◽  
Teis Jensen ◽  
Perrine Knapnougel ◽  
Gwenola Poupon ◽  
...  

2003 ◽  
Vol 77 (17) ◽  
pp. 9412-9421 ◽  
Author(s):  
Mamadi Yilla ◽  
Carole Hickman ◽  
Marcia McGrew ◽  
Elizabeth Meade ◽  
William J. Bellini

ABSTRACT Gamma interferon (IFN-γ) induces expression of the gene products of the major histocompatibility complex (MHC), whereas IFN-α/β can interfere with or suppress class II protein expression. In separate studies, measles virus (MV) was reported to induce IFN-α/β and to up-regulate MHC class II proteins. In an attempt to resolve this paradox, we examined the surface expression of MHC class I and class II proteins in MV-infected peripheral monocytes in the presence and absence of IFN-α/β. Infection of purified monocytes with Edmonston B MV resulted in an apparent increase in cell surface expression of HLA-A, -B, and -C class I proteins, but it had no effect on the expression of HLA-DR class II proteins. MV-infected purified monocytes expressed IFN-α/β, but no measurable IFN-γ expression was detected in supernatant fluids. Class II protein expression could be enhanced by coculture of purified monocytes with uninfected peripheral blood mononuclear cell (PBMC) supernatant. MV infection of PBMCs also did not affect expression of class II proteins, but the expression of HLA-A, -B, and -C class I proteins was increased two- to threefold in most donor cells. A direct role for IFN-α/β suppression of MHC class II protein expression was not evident in monocytes since MV suppressed class II protein expression in the absence of IFN-α/β. Taken together, these data suggest that MV interferes with the expression of peptide-loaded class II complexes, an effect that may potentially alter CD4+-T-cell proliferation and the cell-mediated immune responses that they help to regulate.


Author(s):  
Andrea De Lerma Barbaro ◽  
Giovanna Tosi ◽  
Maria Teresa Valle ◽  
Anna Maria Megiovanni ◽  
Silvia Sartoris ◽  
...  

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