scholarly journals Regulating the retention of T-cell receptor alpha chain variants within the endoplasmic reticulum: Ca(2+)-dependent association with BiP.

1991 ◽  
Vol 114 (2) ◽  
pp. 189-205 ◽  
Author(s):  
C K Suzuki ◽  
J S Bonifacino ◽  
A Y Lin ◽  
M M Davis ◽  
R D Klausner
Keyword(s):  
T Cell ◽  
Cell Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Ionophore A23187 ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Er Retention ◽  
Receptor Alpha Chain

Immunoglobulin heavy chain binding protein (BiP, GRP 78) coprecipitates with soluble and membrane-associated variants of the T-cell antigen receptor alpha chain (TCR-alpha) which are stably retained within the ER. Chelation of Ca2+ during solubilization of cells leads to the dissociation of BiP from the TCR-alpha variants, which is dependent upon the availability of Mg2+ and hydrolyzable ATP; this suggests that Ca2+ levels can serve to modulate the association/dissociation of these proteins with BiP. In vivo treatment of cells expressing either the soluble or membrane-anchored TCR-alpha variants with the Ca2+ ionophore, A23187, or an inhibitor of an ER Ca(2+)-ATPase, thapsigargin, or the membrane-permeant Ca2+ chelator BAPTA-AM, results in the redistribution of these proteins out of the ER and their subsequent secretion or cell surface expression. Under the same assay conditions, no movement of BiP out of the ER is observed. Taken together, these observations indicate that decreased Ca2+ levels result in the dissociation of a protein bound to BiP, leading to its release from ER retention. These data suggest that the intracellular fate of newly synthesized proteins stably associated with BiP can be regulated by Ca2+ levels in the ER.

Expression of T-cell receptor alpha-chain genes in transgenic mice

1988 ◽  
Vol 8 (12) ◽  
pp. 5459-5469
Author(s):  
L J Berg ◽  
B Fazekas de St Groth ◽  
F Ivars ◽  
C C Goodnow ◽  
S Gilfillan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Specific Monoclonal Antibody ◽  
Alpha Chain ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

To examine the influences responsible for shaping the T-cell repertoire in vivo, we have introduced T-cell receptors of defined specificity into mice. In this report, we analyze transgenic mice carrying a T-cell receptor alpha-chain gene from a pigeon cytochrome c-reactive T-cell line. A variant of this construct, which has the immunoglobulin heavy-chain enhancer inserted into the JC intron, was also introduced into mice. Addition of the enhancer increased the steady-state level of transgene-encoded mRNA three- to fivefold in cultured T cells, leading to a two- to threefold increase in surface expression. In vivo, the difference between these two constructs was even more significant, increasing the number of transgene-positive cells from approximately 5 to 70% and the T-cell receptor surface density two- to threefold. Surprisingly, while surface expression of either type of transgene was limited to T cells, we found little tissue specificity with respect to transcription. In T cells expressing the alpha chain from the enhancer-containing construct, immunoprecipitation with a 2B4 alpha-specific monoclonal antibody revealed the expected disulfide-linked dimer. Costaining of these T cells with the 2B4 alpha-specific monoclonal antibody versus anti-CD3 indicated that expression of the transgene-encoded alpha chain precludes expression of endogenous alpha chains on the majority of cells; in contrast, 2B4 alpha-chain expression from the construct lacking the enhancer is inefficient at suppressing endogenous alpha-chain expression. In mice of the enhancer lineage, Southern blot analysis indicated suppression of endogenous alpha-chain rearrangements in T-cell populations, consistent with the observed allelic exclusion at the cellular level. Interestingly, newborn, but not adult, mice of this lineage also showed an increase in retention of unrearranged delta-chain loci in thymocyte DNA, presumably resulting from the suppression of alpha-chain rearrangements. This observation indicates that at least a fraction of alpha:beta-positive T cells have never attempted to produce functional delta rearrangements, thus suggesting that alpha:beta and gamma:delta T cells may be derived from different T-cell compartments (at least during the early phases of T-cell differentiation).

scholarly journals Expression of T-cell receptor alpha-chain genes in transgenic mice.

1988 ◽  
Vol 8 (12) ◽  
pp. 5459-5469 ◽  
Author(s):  
L J Berg ◽  
B Fazekas de St Groth ◽  
F Ivars ◽  
C C Goodnow ◽  
S Gilfillan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Specific Monoclonal Antibody ◽  
Alpha Chain ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

To examine the influences responsible for shaping the T-cell repertoire in vivo, we have introduced T-cell receptors of defined specificity into mice. In this report, we analyze transgenic mice carrying a T-cell receptor alpha-chain gene from a pigeon cytochrome c-reactive T-cell line. A variant of this construct, which has the immunoglobulin heavy-chain enhancer inserted into the JC intron, was also introduced into mice. Addition of the enhancer increased the steady-state level of transgene-encoded mRNA three- to fivefold in cultured T cells, leading to a two- to threefold increase in surface expression. In vivo, the difference between these two constructs was even more significant, increasing the number of transgene-positive cells from approximately 5 to 70% and the T-cell receptor surface density two- to threefold. Surprisingly, while surface expression of either type of transgene was limited to T cells, we found little tissue specificity with respect to transcription. In T cells expressing the alpha chain from the enhancer-containing construct, immunoprecipitation with a 2B4 alpha-specific monoclonal antibody revealed the expected disulfide-linked dimer. Costaining of these T cells with the 2B4 alpha-specific monoclonal antibody versus anti-CD3 indicated that expression of the transgene-encoded alpha chain precludes expression of endogenous alpha chains on the majority of cells; in contrast, 2B4 alpha-chain expression from the construct lacking the enhancer is inefficient at suppressing endogenous alpha-chain expression. In mice of the enhancer lineage, Southern blot analysis indicated suppression of endogenous alpha-chain rearrangements in T-cell populations, consistent with the observed allelic exclusion at the cellular level. Interestingly, newborn, but not adult, mice of this lineage also showed an increase in retention of unrearranged delta-chain loci in thymocyte DNA, presumably resulting from the suppression of alpha-chain rearrangements. This observation indicates that at least a fraction of alpha:beta-positive T cells have never attempted to produce functional delta rearrangements, thus suggesting that alpha:beta and gamma:delta T cells may be derived from different T-cell compartments (at least during the early phases of T-cell differentiation).

scholarly journals Deletional rearrangement in the human T-cell receptor alpha-chain locus.

1987 ◽  
Vol 84 (23) ◽  
pp. 8608-8612 ◽  
Author(s):  
J. P. de Villartay ◽  
D. Lewis ◽  
R. Hockett ◽  
T. A. Waldmann ◽  
S. J. Korsmeyer ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Chain Locus ◽  
Human T Cell ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

scholarly journals Diversity and structure of human T-cell receptor alpha-chain variable region genes.

1987 ◽  
Vol 84 (19) ◽  
pp. 6884-6888 ◽  
Author(s):  
M. H. Klein ◽  
P. Concannon ◽  
M. Everett ◽  
L. D. Kim ◽  
T. Hunkapiller ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Variable Region ◽  
Cell Receptor ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Human T Cell ◽  
Variable Region Genes ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

scholarly journals T cell receptor alpha chain genes are located on chromosome 14 at 14q11-14q12 in humans.

1985 ◽  
Vol 161 (5) ◽  
pp. 1255-1260 ◽  
Author(s):  
N Caccia ◽  
G A Bruns ◽  
I R Kirsch ◽  
G F Hollis ◽  
V Bertness ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chromosome 14 ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Human T Cell ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

A cDNA clone encoding the alpha chain of the human T cell receptor was used in connection with somatic cell human-rodent hybrids to determine that the genes coding for the alpha chain are located on chromosome 14 in humans. In situ hybridization confirms this result and further localizes these genes to 14q11-14q12 on this chromosome. Since this region of chromosome has been shown to be nonrandomly involved in a number of T cell neoplasias, this assignment raises a number of interesting questions as to the possible involvement of the T cell receptor alpha chain genes in tumorigenesis.

Discordance of the T-cell receptor alpha-chain gene in familial multiple sclerosis

Neurology ◽  
1992 ◽  
Vol 42 (4) ◽  
pp. 839-839 ◽  
Author(s):  
S. G. Lynch ◽  
J. W. Rose ◽  
J. H. Petajan ◽  
M. Leppert
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha

Structure and organization of the T cell receptor alpha chain genes in Atlantic salmon

2004 ◽  
Vol 41 (5) ◽  
pp. 553-559 ◽  
Author(s):  
Ivar Hordvik ◽  
Jannicke Torvund ◽  
Lindsey Moore ◽  
Curt Endresen
Keyword(s):  
T Cell ◽  
Atlantic Salmon ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Alpha ◽  
Alpha Chain ◽  
Receptor Alpha Chain ◽  
Cell Receptor Alpha
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