scholarly journals Predominant expression of a T cell receptor V beta gene subfamily in autoimmune encephalomyelitis.

1988 ◽  
Vol 167 (5) ◽  
pp. 1586-1596 ◽  
Author(s):  
S S Zamvil ◽  
D J Mitchell ◽  
N E Lee ◽  
A C Moore ◽  
M K Waldor ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
T Cell Response ◽  
Chain Gene ◽  
Beta Chain ◽  
Autoimmune Encephalomyelitis ◽  
Cell Clones ◽  
Beta Chain Genes

TCR beta chain gene expression of individual T cell clones that share the same MHC class II restriction and similar fine specificity for the encephalitogenic NH2 terminus of the autoantigen myelin basic protein (MBP) has been examined. TCR V beta expression was examined by FACS analysis with mAbs specific for the V beta 8 subfamily of TCR beta chain genes. 14 of 18 (78%) NH2-terminal MBP-specific clones examined express a member of the TCR V beta 8 subfamily. Southern analysis was used to identify which member(s) of the TCR V beta 8 subfamily is expressed by these clones. Each of four clones examined uses V beta 8.2, though two different V beta 8.2-J beta 2 combinations were identified. Our findings indicate that there is restricted TCR V beta usage in the autoimmune T cell response to the dominant encephalitogenic NH2-terminal epitope of the MBP. The use of an mAb to the antigen-specific TCR in the prevention of T cell-mediated autoimmune disease has been investigated. Our results demonstrate that in vivo administration of a TCR V beta 8-specific mAb prevents induction of autoimmune encephalomyelitis.

scholarly journals Correlation of T cell receptor V beta gene family with MHC restriction.

1987 ◽  
Vol 166 (2) ◽  
pp. 583-588 ◽  
Author(s):  
P A Morel ◽  
A M Livingstone ◽  
C G Fathman
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Sperm Whale ◽  
Cell Receptor ◽  
Chain Gene ◽  
Beta Chain ◽  
T Cell Clones ◽  
Mhc Restriction ◽  
Cell Clones ◽  
Beta Chain Genes

We have studied a panel of DBA/2 T cell clones specific for sperm whale myoglobin (SpW Mb) for TCR (T cell receptor) beta chain gene expression by FACS analysis using the monoclonal antibodies F23.1 and KJ16 specific for the V beta 8 family of the TCR beta chain genes. Within any given specificity group, all the clones tested came from different mice. 10 of 11 I-Ed-restricted SpW Mb-specific T cell clones were F23.1+; 8 of these were also KJ16+. Only one of the three I-Ad-restricted clones tested was F23.1+; this clone was KJ16 negative. This study has demonstrated that I-Ed-restricted T cell clones from DBA/2 mice express members of the TCR V beta 8 family irrespective of the epitopes of SpW Mb recognized. These data suggest an apparent correlation between TCR V beta expression and MHC restriction.

scholarly journals p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene.

1993 ◽  
Vol 90 (7) ◽  
pp. 2685-2689 ◽  
Author(s):  
H. Messier ◽  
T. Fuller ◽  
S. Mangal ◽  
H. Brickner ◽  
S. Igarashi ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Beta Chain ◽  
T Cell Receptor Beta ◽  
Receptor Beta

scholarly journals Human acute unclassified leukemia with a unique t(4;17) chromosomal translocation expresses T lymphoid and myeloid surface antigens after in vitro culture

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 271-277 ◽  
Author(s):  
A Ganser ◽  
G Heil ◽  
T Bohm ◽  
CR Bartram ◽  
A Raghavachar ◽  
...  
Keyword(s):  
T Cell ◽  
Suspension Culture ◽  
T Cell Receptor ◽  
Heavy Chain ◽  
Cell Receptor ◽  
Beta Chain ◽  
T Cell Receptor Beta ◽  
Beta Chain Genes ◽  
Receptor Beta

Abstract Bilineage differentiation along both the T lymphoid and the myeloid lineage while in in vivo diffusion chamber (DC) and in vitro suspension culture was observed in a case of acute unclassified leukemia (null-AL) and t(4;17). Prior to culture, the blast cells were TdT and la positive but did not express any lineage-specific antigenic markers. Furthermore, the immunoglobulin heavy chain and T cell receptor beta- chain genes were in germline configuration. Cytogenetically, all metaphases had the unique translocation t(4;17) (q25;q23) prior to and after culture, supporting the leukemic origin of the cells. During both DC culture and suspension culture with and without tetradecanoyl- phorbol-acetate (TPA), a substantial increase in the absolute and relative number of cells expressing both myeloid and T lymphoid antigenic markers occurred. Double-fluorescence analysis demonstrated the expression of antigenic markers of both lineages on the same population of cells, and electron microscopy revealed the induction of myeloperoxidase after both DC and suspension culture. Immunoglobulin heavy chain and T cell receptor beta-chain genes remained in germline configuration after treatment with TPA, when analyzed with JH and CT beta probes, respectively. These findings indicate that this case represents a null-AL with dual-lineage capabilities, which has probably arisen from the malignant transformation of a bipotential stem cell of lymphoid and myeloid progeny.

scholarly journals T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1472-1483 ◽  
Author(s):  
A Bonati ◽  
P Zanelli ◽  
S Ferrari ◽  
A Plebani ◽  
B Starcich ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gene Transcript ◽  
Beta Chain ◽  
Early Stages ◽  
Human Thymus ◽  
Nucleotide Insertions ◽  
Beta Gene

Abstract T-cell receptor (TCR) beta-chain proteins appear early (approximately 15th week of gestation) during human thymic ontogenesis. These beta- chain proteins, which appear before terminal deoxynucleotidyl transferase (TdT), could be an expression of a fully rearranged (V-D- J), incompletely rearranged (D-J), or germline TCR beta-chain gene. The aims of this study, performed from the 15th week onward, were the following: (1) to investigate whether or not TCR beta gene rearranges at an early stage during human thymic ontogenesis; (2) to investigate whether complete presumptive functional (1.3 kb) TCR beta gene transcript is present at these early stages of development, or if incomplete (1 kb) or germ-line (1.1 kb) transcripts are expressed; (3) to examine the phenotype of TCR beta-chain+ cells with two-color fluorescence using monoclonal antibody (MoAb) beta F1 and MoAbs that recognize CD1, CD2, CD3, CD4, CD8, CD5, and CD7 antigens (rabbit anti- calf TdT antiserum was used to detect TdT); and (4) to demonstrate whether or not beta gene N-diversity regions are detectable as early as the 15th week and whether or not N-nucleotide insertions correlate to TdT expression. Fifteen- to 22-week fetal thymuses and pediatric thymuses were investigated. We demonstrated that TCR beta-chain gene rearranged as early as the 15th week in human thymus and that a complete functional TCR beta gene transcript was expressed at these early stages of human development. No other analyses to date have investigated TCR beta gene expression in early human thymus using molecular biology techniques. No significant differences were detectable between phenotypic analysis of fetal and pediatric samples, except for TdT expression, which appeared after the 20th week. Essentially all mCD3+ (OKT3+) cells were beta-chain+ at the different weeks investigated. A significant percentage of CD1+ cells were beta- chain+, and the percentage increased along with the age of development. After the 20th week, we identified three main populations: TdT+, cCD3+, beta F-(early thymic precursors); TdT+, CD1+, beta F1+ (intermediate maturity cortical thymocytes); and TdT-, mCD3+, beta F1++ (mature medullary thymocytes). Given these values, we may consider beta-chain expression an ordered process. beta gene N-nucleotide insertions were correlated to TdT expression, since N-regions increased considerably after the 20th week. A further increase of N-nucleotide insertions was detected from the 22nd week to the 32nd week.

scholarly journals Expression of T cell receptor genes in an antigen-specific hybridoma and radiation-induced variants.

1986 ◽  
Vol 164 (1) ◽  
pp. 113-130 ◽  
Author(s):  
N R Gascoigne ◽  
S Waters ◽  
J F Elliott ◽  
C Victor-Kobrin ◽  
C Goodnow ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Antigenic Determinants ◽  
Beta Chain ◽  
Stable Production ◽  
Radiation Induced ◽  
V Region ◽  
Beta Chain Genes ◽  
Antigen Reactivity

We have analyzed a series of mutants derived from a KLH-specific, I-E-restricted T hybridoma (FN1-18) which have lost antigen-reactivity while retaining both T cell receptor idiotypic determinants and the ability to respond to Con A. The variants have not gained any detectable alloreactivity, nor is there an obvious lesion in the mutants' beta chain DNA containing the utilized beta chain genes. This loss of antigen reactivity is due to a failure of stable production of the specific V beta-containing mRNA. Our results indicate that in FN1-18, the T cell receptor antigenic determinants are most likely carried by the alpha chain alone or by a complementation product of the V alpha FN1-18 with the V beta of BW5147. V beta FN1-18 represents a previously undescribed T cell receptor V region.

scholarly journals Generation of diversity in T cell receptor repertoire specific for pigeon cytochrome c.

1987 ◽  
Vol 165 (2) ◽  
pp. 279-301 ◽  
Author(s):  
S B Sorger ◽  
S M Hedrick ◽  
P J Fink ◽  
M A Bookman ◽  
L A Matis
Keyword(s):  
T Cell ◽  
Cytochrome C ◽  
T Cell Receptor ◽  
Cell Lines ◽  
Dna Sequences ◽  
Cell Receptor ◽  
T Cell Response ◽  
Beta Chain ◽  
Antigen Specificity ◽  
T Cell Lines

17 T cell clones and 3 T cell lines, specific for pigeon cytochrome c, were analyzed for fine specificity and rearranged T cell receptor (TCR) gene elements. Clones of similar fine specificities were grouped into one of four phenotypes, and correlations between phenotype differences and gene usage could be made. All the lines and clones rearranged a member of the V alpha 2B4 gene family to a limited number of J alpha regions. The beta chain was made up of one of three non-cross-hybridizing V beta regions, each rearranging to only one or two J beta s. The use of alternate V beta regions could be correlated with phenotype differences, which were manifested either as MHC- or MHC and antigen-specificity changes. In addition, the presence of alloreactivity, which defined a phenotype difference, could be correlated solely with the use of an alternate J alpha region. These observations were substantiated by prospective analyses of pigeon cytochrome c-specific T cell lines that were selected for alternate MHC specificity or alloreactivity and were found to express the correlated alpha and beta chain rearrangements. Previously, the TCR DNA sequences from two clones, each representing a variant of one phenotype, showed sequence differences only in the N regions of their TCR genes. Since only these two variants, using identical V alpha-J alpha and V beta-J beta gene elements, were repeatedly observed in this study, we would predict that the junctional diversity differences are selectable. In this T cell response, all the gene elements involved in the generation of diversity appear to be selected, and may therefore be important in the determination of TCR specificity. This high degree of receptor gene selection represents a fundamental difference from the diversity seen in several extensively analyzed antibody responses.

scholarly journals Rearrangement of T-cell receptor beta-chain genes during T-cell development.

1985 ◽  
Vol 82 (9) ◽  
pp. 2925-2929 ◽  
Author(s):  
W. Born ◽  
J. Yague ◽  
E. Palmer ◽  
J. Kappler ◽  
P. Marrack
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Development ◽  
Cell Receptor ◽  
Cell Development ◽  
Beta Chain ◽  
T Cell Receptor Beta ◽  
Beta Chain Genes ◽  
Receptor Beta

scholarly journals Human T cell gamma genes are frequently rearranged in B-lineage acute lymphoblastic leukemias but not in chronic B cell proliferations.

1987 ◽  
Vol 165 (4) ◽  
pp. 1000-1015 ◽  
Author(s):  
Z Chen ◽  
D Le Paslier ◽  
J Dausset ◽  
L Degos ◽  
G Flandrin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Gene Rearrangement ◽  
Chain Gene ◽  
Beta Chain ◽  
Surface Phenotype ◽  
Chain Gene Rearrangement ◽  
B Lineage ◽  
Beta Chain Genes

T cell rearranging gene gamma (TRG gamma) and T cell antigen receptor beta (TCR beta) chain gene rearrangement and transcription were studied in a series of patients with B-lineage acute lymphoblastic leukemia (ALL), in which the Ig H chain genes are rearranged and the surface phenotype reproduces the stages of normal pre-B maturation. For comparison, polyclonal T cells from peripheral blood of healthy donors and blast cells from 19 cases of T lineage ALL were also studied. In this study we demonstrate the presence of a clonal rearrangement of the TRG gamma in 18 of the 22 B-lineage ALL cases and establish that this rearrangement, which generally involves the J gamma 1 region, is often monoallelic and appears different from the biallelic J gamma 2 rearrangement frequently seen in T-cell ALLs. In 9 of 22 cases, we found rearrangement of the genes of the TCR beta chain, which never involved the J beta 1 region. Conversely, the TRG gamma were seen in germline configuration in all 19 cases of B chronic lymphoid malignancies. In none of the 9 AML cases studied was TRG gamma and TCR beta chain gene rearrangement found. The TCR beta chain genes were rearranged in one B cell chronic lymphocytic leukemia (CLL). We also show that in B-lineage ALL, the cells probably use the same V gamma genes for TRG gamma rearrangements as the malignant cells in T-ALL and the polyclonal T cells. In none of the 13 B-lineage ALL cases investigated by Northern analysis was TCR beta mRNA expression detected, whereas a weak expression of TRG gamma transcripts was found in two of these cases. The correlations between surface phenotype, rearrangement of TRG gamma, TCR beta, and Ig H chain genes were analyzed. The significance of rearrangement of TRG gamma and TCR beta chain genes in B or pre-B cells is also discussed.

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