203 research outputs found
Sequence of the mouse Q4 class I gene and characterization of the gene product
The Q4 class I gene has been shown to participate
in gene conversion events within the mouse major
histocompatibility complex. Its complete genomic nucleotide
sequence has been determined. The 5' half of Q4
resembles H-2 genes more strongly than other Q genes.
Its 3' end, in contrast, is Q-like and contains a translational
stop signal in exon 5 which predicts a polypeptide with
an incomplete membrane spanning segment. The presence
of two inverted B1 repeats suggests that part of the Q4
gene may be mobile within the genome. Gene transfer experiments
have shown that the Q4 gene encodes a
ß2-microglobulin associated polypeptide of Mr 41 000. A
similar protein was found in activated mouse spleen cells.
The Q4 polypeptide was found to be secreted both by
spleen cells and by transfected fibroblasts and was not detectable
on the cell surface. Antibody binding and twodimensional
gel electrophoresis indicate that the Q4
molecule is identical to a mouse class I polypeptide, Qb-1,
which has been previously described
A Nonpolymorphic Class I Gene in the Murine Major Histocompatibility Complex
DNA sequence analysis of a class I gene (QlO), which maps to the Qa2,3 locus in the C57BL/lO (H-
2b haplotype) mouse, reveals that it is almost identical
to a cDNA clone (pH16) isolated from a SWR/J
(H-2q haplotype) mouse liver cDNA library. Exon 5,
in particular, has an unusual structure such that a
polypeptide product is unlikely to be anchored in the
cell membrane. Our findings suggest that the two
sequences are derived from allelic class I genes,
which are nonpolymorphic, in contrast to H-2K allelic
sequences from the same mice, and they may encode
liver-specific polypeptides of unknown function.
Our previous studies indicate that the QlO gene
is a potential donor gene for the generation of mutations
at the H-2K locus by inter-gene transfer of
genetic information. Thus the lack of polymorphism
in class I genes at the QlO locus implies either that
they are not recipients for such exchanges or that
selective pressure prevents the accumulation of mutations
in genes at this locus
Regulation of prostaglandin synthesis and cell adhesion by a tryptophan catabolizing enzyme
BACKGROUND: The tryptophan catabolizing enzyme, indoleamine 2,3, dioxygenase (IDO) is one of two mammalian enzymes, which can catabolize the rarest essential amino acid, tryptophan. IDO is inducible by cytokines such as interferon-γ and plays a role in inflammation and maternal tolerance of fetal allografts, although its exact mode of action is unclear. Therefore, we investigated the circumstances under which IDO is expressed in vitro together with the effects of overexpression of IDO on the growth and morphology of cells. RESULTS: Overexpression of IDO in the murine macrophage cell line RAW 264.7 and the murine fibrosarcoma cell line MC57, resulted in the growth of macroscopic cell foci, with altered cell adhesion properties. The expression of IDO was also detected during adhesion of wild type, nontransfected cells in tissue culture to standard cell growth substrates. Inhibition of this expression, likewise resulted in alterations in cell adhesion. Overexpression of IDO or inhibition of endogenous IDO expression was accompanied by changes in metalloproteinase expression and also in the expression and activity of the cyclooxygenase enzymes. In the case of RAW cells, IDO effects on cell growth could be reversed by adding back prostaglandins. CONCLUSIONS: These results suggest that catabolism of the rarest essential amino acid may regulate processes such as cell adhesion and prostaglandin synthesis
Altered Tryptophan Metabolism as a Paradigm for Good and Bad Aspects of Immune Privilege in Chronic Inflammatory Diseases
The term “immune privilege” was coined to describe weak immunogenicity (hypo-immunity) that manifests in some transplant settings. We extended this concept to encompass hypo-immunity that manifests at local sites of inflammation relevant to clinical diseases. Here, we focus on emerging evidence that enhanced tryptophan catabolism is a key metabolic process that promotes and sustains induced immune privilege, and discuss the implications for exploiting this knowledge to improve treatments for hypo-immune and hyper-immune syndromes using strategies to manipulate tryptophan metabolism
Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA
Transformation of murine thymocytes by
radiation leukemia virus is associated with reduced expression
of the class I antigens encoded in the major histocompatibility
complex (MHC) and increased methylation and altered restriction
enzyme patterns of MHC DNA. These changes may play
a role in host susceptibility to virus-induced leukemogenesis
and accord with the notion that viral genomes play a regulatory
function when they integrate adjacent to histocompatibiity
genes
Structure and expression of the human globin genes and murine histocompatibility antigen genes
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