2,133 research outputs found
VH-RELATED IDIOTOPES DETECTED BY SITE-DIRECTED MUTAGENESIS
The function of the CD4 cell surface protein as
coreceptor on T helper lymphocytes and as receptor
for HIV makes this glycoprotein a prime target for
an immune intervention with mAb. A detailed understanding
of the structural determinants on the
therapeutic CD4 mAb that are involved in Ag binding
or are recognized by anti-idiotypic mAb (anti-Id)
may be important for designing antibodies with optimal
therapeutic efficacy. Seven anti-Id raised
against the CD4 mAb M-T310 were selected from a
large panel with the intention to obtain CD4 mimicking
structures with specificity foHr IV gp120. The
selected anti-Id did not reacwt ith other CDCspecific
mAb cross-blocking M-T310. Among these, mAb MT404,
although having the same L chain as M-T310
and a VH region sequence differing onlya t 14 amino
acid positions, was not recognized by the anti-Id. MT310
H chain complexed with the J558L L chain
reacted with all anti-Id, thus demonstrating that the
recognized idiotopes are located within the VH region.
To identify the idiotopes of M-T310 seen by
the anti-Id, variants of M-T404 containing one or
more of the M-T3 1 O-derived substitutions were generated
by oligonucleotide-directed mutagenesis.
The reactivity pattern of the mutant proteins with
the anti-Id demonstrated that the idiotopes reside
within the complementarity determining region
(CDR) 2 and CDR3 loops of the VH region. A major
idiotope was definebdy a single amino acid in CDR2
that was recognized by three anti-Id, whereas the
four other anti-Id reacted with determinants of
CDR3. Although the performed amino acid substitutions
did influence the Id recognition, Ag binding
was not significantly affected, suggesting that none
of the anti-Id can be considered as a mimicry of the
CD4 A
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
THE CELLULAR RECEPTOR (CD4) OF THE HUMAN IMMUNODEFICIENCY VIRUS IS EXPRESSED ON NEURONS AND GLIAL CELLS IN HUMAN BRAIN
The peculiar tropism of the human immunodeficiency virus (HIV) for T
helper lymphocytes can be explained by a specific interaction between the virus
and the CD4 molecule on these cells (1, 2). The tropism for T lymphocytes,
however, can hardly account for the early brain infection observed in some AIDS
(acquired immune deficiency syndrome) patients (3, 4). Since CD4 is also expressed
on virus-susceptible non-T cell lines we wondered whether an additional
expression site of CD4 could be demonstrated in neural tissue (5). To this end,
CD4 expression in brain was analyzed with several different anti-CD4 mAbs, and
using a CD4-specific cDNA probe in Northern blot analyses . CD4' cells and
CD4-specific mRNA were found in the cerebellum, thalamus, and pons. The
reactive cells could be identified as neurons as well as glial cells
Universality in Random Walk Models with Birth and Death
Models of random walks are considered in which walkers are born at one
location and die at all other locations with uniform death rate. Steady-state
distributions of random walkers exhibit dimensionally dependent critical
behavior as a function of the birth rate. Exact analytical results for a
hyperspherical lattice yield a second-order phase transition with a nontrivial
critical exponent for all positive dimensions . Numerical studies
of hypercubic and fractal lattices indicate that these exact results are
universal. Implications for the adsorption transition of polymers at curved
interfaces are discussed.Comment: 11 pages, revtex, 2 postscript figure
Imaging ellipsometry of graphene
Imaging ellipsometry studies of graphene on SiO2/Si and crystalline GaAs are
presented. We demonstrate that imaging ellipsometry is a powerful tool to
detect and characterize graphene on any flat substrate. Variable angle
spectroscopic ellipsometry is used to explore the dispersion of the optical
constants of graphene in the visible range with high lateral resolution. In
this way the influence of the substrate on graphene's optical properties can be
investigatedComment: 3 pages, 3 figure
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Glycogen synthase kinases 3α and 3β in cardiac myocytes: regulation and consequences of their inhibition
Inhibition of glycogen synthase kinase 3β (GSK3β) as a consequence of its phosphorylation by protein kinase B/Akt (PKB/Akt) has been implicated in cardiac myocyte hypertrophy in response to endothelin-1 or phenylephrine. We examined the regulation of GSK3α (which we show to constitute a significant proportion of the myocyte GSK3 pool) and GSK3β in cardiac myocytes. Although endothelin increases phosphorylation of GSK3 and decreases its activity, the response is less than that induced by insulin (which does not promote cardiac myocyte hypertrophy). GSK3 phosphorylation induced by endothelin requires signalling through the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade and not the PKB/Akt pathway, whereas the reverse is true for insulin. Cardiac myocyte hypertrophy involves changes in morphology, and in gene and protein expression. The potent GSK3 inhibitor 1-azakenpaullone increases myocyte area as a consequence of increased cell length whereas phenylephrine increases both length and width. Azakenpaullone or insulin promotes AP1 transcription factor binding to an AP1 consensus oligonucleotide, but this was significantly less than that induced by endothelin and derived principally from increased binding of JunB protein, the expression of which was increased. Azakenpaullone promotes significant changes in gene expression (assessed by Affymetrix microarrays), but the overall response is less than with endothelin and there is little overlap between the genes identified. Thus, although GSK3 may contribute to cardiac myocyte hypertrophy in some respects (and presumably plays an important role in myocyte metabolism), it does not appear to contribute as significantly to the response induced by endothelin as has been maintained
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Priming letters by colors: evidence for the bidirectionality of grapheme–color synesthesia
In synesthesia, stimulation of one sensory modality leads to a percept in another nonstimulated modality, for example, graphemes trigger an additional color percept in grapheme–color synesthesia, which encompasses the variants letter–color and digit–color synesthesia. Until recently, it was assumed that synesthesia occurs strictly unidirectional: Although the perception of a letter induces a color percept in letter–color synesthetes, they typically do not report that colors trigger the percept of a letter. Recent data on number processing in synesthesia suggest, however, that colors can implicitly elicit numerical representations in digit–color synesthetes, thereby questioning unidirectional models of synesthesia. Using a word fragment completion paradigm in 10 letter–color synesthetes, we show here for the first time that colors can implicitly influence lexical search. Our data provide strong support for a bidirectional nature of grapheme–color synesthesia and, in general, may allude to the mechanisms of cross-modality interactions in the human brain
Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the a-chain of the human interleukin-2 receptor
The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of
them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized
two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs
are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human
complement, the individual Abs are negative; however, when used in combination, complement activation was performed.
When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display
this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by
combination of an anti-CD4 mAb with one directed against the a-chain of the human IL2 receptor, nearly 100% inhibition
of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4
mAb and an anti-IL2Rcc chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating
that this mAb cocktail could be a new strategy for immunosuppressive therapy
EXPRESSION OF A FUNCTIONAL CHIMERIC lg-MHC CLASS II PROTEIN
composed of the a- and ß-chains of the MHC class I1
I-E molecule fused to antibody V regions derived
from anti-human CD4 mAb MT310. Expression vectors
were constructed containing the functional,
rearranged gene segments coding for the V region
domains of the antibody H and L chains in place of
the first domains of the complete structural genes
of the I-E a- and ß-chains, respectively. Celltsr ansfected
with both hybrid genes expressed a stable
protein product on the cell surface. The chimeric
molecule exhibited the idiotype of the antibody
MT310 as shown by binding to the anti-idiotypic
mAb 20-46. A protein of the anticipated molecular
mass was immunoprecipitated witha nti-mouse IgG
antiserum. Furthermore, human soluble CD4 did
bind to thetr ansfected cell line, demonstrating that
the chimeric protein possessed the binding capacity
of the original mAb. Thus, the hybrid molecule retained:
1) the properties of a MHC class I1 protein
with regardt o correct chain assembly and transport
to the cell surface: as well as 2) the Ag binding
capacity of the antibody genes used. Thgee neration
of hybrid MHC class I1 molecules with highly specific,
non-MHC-restricted bindingc apacities will be
useful for studying MHC class 11-mediated effector
functions such as selection of the T cell repertoire
in thymus of transgenic mice
Is the dynamics of open quantum systems always linear?
We study the influence of the preparation of an open quantum system on its
reduced time evolution. In contrast to the frequently considered case of an
initial preparation where the total density matrix factorizes into a product of
a system density matrix and a bath density matrix the time evolution generally
is no longer governed by a linear map nor is this map affine. Put differently,
the evolution is truly nonlinear and cannot be cast into the form of a linear
map plus a term that is independent of the initial density matrix of the open
quantum system. As a consequence, the inhomogeneity that emerges in formally
exact generalized master equations is in fact a nonlinear term that vanishes
for a factorizing initial state. The general results are elucidated with the
example of two interacting spins prepared at thermal equilibrium with one spin
subjected to an external field. The second spin represents the environment. The
field allows the preparation of mixed density matrices of the first spin that
can be represented as a convex combination of two limiting pure states, i.e.
the preparable reduced density matrices make up a convex set. Moreover, the map
from these reduced density matrices onto the corresponding density matrices of
the total system is affine only for vanishing coupling between the spins. In
general, the set of the accessible total density matrices is nonconvex.Comment: 19 pages, 3 figures, minor changes to improve readability, discussion
on Mori's linear regime and references adde
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