scholarly journals A novel subset of human lymphocytes with a T cell receptor-gamma complex.

1987 ◽  
Vol 166 (4) ◽  
pp. 1192-1197 ◽  
Author(s):  
S Jitsukawa ◽  
F Faure ◽  
M Lipinski ◽  
F Triebel ◽  
T Hercend
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Human Lymphocytes ◽  
Cell Receptor ◽  
Surface Expression ◽  
Gamma Chain ◽  
A Cells ◽  
Wide Range ◽  
Circulating Lymphocytes ◽  
Alpha Beta

We have previously characterized a CD3+ T cell receptor (TCR) alpha/beta- human fetal cloned cell line, termed F6C7, which surface-expresses a CD3-associated gamma chain identified by anti-NKFi, an mAb with a restricted clonotypic reactivity. Here, we have produced an additional antibody, anti-Ti-gamma A, which recognizes a public epitope of the gamma molecule defined by anti-NKFi. Ti-gamma A is present on approximately 3% of circulating lymphocytes with a wide range (1-15%) among 30 healthy individuals tested. Two-color immunofluorescence experiments performed with anti-Ti-gamma A and BMA 031 mAb (a reagent specific for the TCR-alpha/beta receptor) showed that surface expression of Ti-alpha/beta and Ti-gamma A is mutually exclusive. Moreover, it was found that most Ti-gamma A+ cells are CD2+, CD3+, CD4-, CD5+, NKH1-, HLA class II-negative. In contrast, the expression of the CD8 molecule on these T lymphocytes appears to be variable from one individual to another. Finally, we found that Ti-gamma A+ cells represent a majority of peripheral lymphocytes that express CD3 proteins but not the TCR-alpha/beta heterodimer. The delineation of this unique lymphocyte subset should help further studies on the biology of cells with a CD3-associated gamma complex.

scholarly journals Surface expression of functional T cell receptor chains formed by interlocus recombination on human T lymphocytes.

1994 ◽  
Vol 180 (5) ◽  
pp. 1685-1691 ◽  
Author(s):  
F Davodeau ◽  
M A Peyrat ◽  
J Gaschet ◽  
M M Hallet ◽  
F Triebel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Structural Features ◽  
Gamma Delta ◽  
Cell Repertoire ◽  
Repertoire Selection ◽  
Alpha Beta

Structural diversity of lymphocyte antigen receptors (the immunoglobulin [Ig] of B cells and the alpha/beta or gamma/delta T cell receptor [TCR] of T cells) is generated through somatic rearrangements of V, D, and J gene segments. Classically, these recombination events involve gene segments from the same Ig or TCR locus. However, occurrence of "trans" rearrangements between distinct loci has also been described, although in no instances was the surface expression of the corresponding protein under normal physiological conditions demonstrated. Here we show that hybrid TCR genes generated by trans rearrangement between V gamma and (D) J beta elements are translated into functional antigen receptor chains, paired with TCR alpha chains. Like classical alpha/beta T cells, cells expressing these hybrid TCR chains express either CD4 or CD8 coreceptors and are frequently alloreactive. These results have several implications in terms of T cell repertoire selection and relationships between TCR structure and specificity. First, they suggest that TCR alloreactivity is determined by the repertoire selection processes operating during lymphocyte development rather than by structural features specific to V alpha V beta regions. Second, they suggest the existence of close structural relationships between gamma/delta and alpha/beta TCR and more particularly, between V gamma and V beta regions. Finally, since a significant fraction of PBL (at least 1/10(4)) expressed hybrid TCR chains on their surface, these observations indicate that trans rearrangements significantly contribute to the combinatorial diversification of the peripheral immune repertoire.

scholarly journals Fc gamma RII/III and CD2 expression mark distinct subpopulations of immature CD4-CD8- murine thymocytes: in vivo developmental kinetics and T cell receptor beta chain rearrangement status.

1993 ◽  
Vol 177 (4) ◽  
pp. 1079-1092 ◽  
Author(s):  
H R Rodewald ◽  
K Awad ◽  
P Moingeon ◽  
L D'Adamio ◽  
D Rabinowitz ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Fetal Development ◽  
Cell Receptor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Immunoglobulin Gene ◽  
Beta Chain ◽  
Double Positive ◽  
Alpha Beta

We have recently identified a dominant wave of CD4-CD8- (double-negative [DN]) thymocytes in early murine fetal development that express low affinity Fc gamma receptors (Fc gamma RII/III) and contain precursors for Ti alpha/beta lineage T cells. Here we show that Fc gamma RII/III is expressed in very immature CD4low single-positive (SP) thymocytes and that Fc gamma RII/III expression is downregulated within the DN subpopulation and before the CD3-CD8low SP stage in T cell receptor (TCR)-alpha/beta lineage-committed thymocytes. DN Fc gamma RII/III+ thymocytes also contain a small fraction of TCR-gamma/delta lineage cells in addition to TCR-alpha/beta progenitors. Fetal day 15.5 DN TCR-alpha/beta lineage progenitors can be subdivided into three major subpopulations as characterized by cell surface expression of Fc gamma RII/III vs. CD2 (Fc gamma RII/III+CD2-, Fc gamma RII/III+CD2+, Fc gamma RII/III-CD2+). Phenotypic analysis during fetal development as well as adoptive transfer of isolated fetal thymocyte subpopulations derived from C57B1/6 (Ly5.1) mice into normal, nonirradiated Ly5.2 congenic recipient mice identifies one early differentiation sequence (Fc gamma RII/III+CD2(-)-->Fc gamma RII/III+CD2(+)-->Fc gamma RII/III-CD2+) that precedes the entry of DN thymocytes into the CD4+CD8+ double-positive (DP) TCRlow/- stage. Unseparated day 15.5 fetal thymocytes develop into DP thymocytes within 2.5 d and remain at the DP stage for > 48 h before being selected into either CD4+ or CD8+ SP thymocytes. In contrast, Fc gamma RII/III+CD2- DN thymocytes follow this same developmental pathway but are delayed by approximately 24 h before entering the DP compartment, while Fc gamma RII/III-CD2+ display accelerated development by approximately 24 h compared with total day 15.5 thymocytes. Fc gamma RII/III-CD2+ are also more developmentally advanced than Fc gamma RII/III+CD2- fetal thymocytes with respect to their TCR beta chain V(D)J rearrangement. At day 15.5 in gestation, beta chain V(D)J rearrangement is mostly, if not entirely, restricted to the Fc gamma RII/III-CD2+ subset of DN fetal thymocytes. Consistent with this analysis in fetal thymocytes, > 90% of adult thymocytes derived from mice carrying a disrupting mutation at the recombination-activating gene 2 locus (RAG-2-/-) on both alleles are developmentally arrested at the DN CD2- stage. In addition, there is a fivefold increase in the relative percentage of thymocytes expressing Fc gamma RII/III in TCR and immunoglobulin gene rearrangement-incompetent homozygous RAG-2-/- mice (15% Fc gamma RII/III+) versus rearrangement-competent heterozygous RAG-2+/- mice (< 3% Fc gamma RII/III+). Thus, Fc gamma RII/III expression defines an early DN stage preceding V beta(D beta)I beta rearrangement, which in turn is followed by surface expression of CD2. Loss of Fc gamma RII/III and acquisition of CD2 expression characterize a late DN stage immediately before the conversion into DP thymocytes.

scholarly journals Surface expression of a T cell receptor beta (TCR-beta) chain in the absence of TCR-alpha, -delta, and -gamma proteins.

1991 ◽  
Vol 174 (4) ◽  
pp. 775-783 ◽  
Author(s):  
J A Punt ◽  
R T Kubo ◽  
T Saito ◽  
T H Finkel ◽  
S Kathiresan ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Transmembrane Proteins ◽  
Cell Receptor ◽  
Surface Expression ◽  
Gamma Delta ◽  
Cell Interior ◽  
T Cell Receptor Beta ◽  
Alpha Beta ◽  
Receptor Beta

The antigen receptor expressed by mature T cells has been described as a disulfide-linked alpha/beta or gamma/delta heterodimer noncovalently associated with CD3, a complex of transmembrane proteins that communicates signals from the T cell receptor (TCR) to the cell interior. Studies suggest that all component chains must assemble intracellularly before surface expression can be achieved. We described, however, a CD4+/CD8+ transformed murine thymocyte, KKF, that expresses surface TCR-beta chains in the absence of gamma, delta, and alpha proteins; these beta chains are only weakly associated with CD3-epsilon and CD3-zeta. Furthermore, KKF responds differently to stimulation through TCR-beta and CD3-epsilon, a functional dissociation that has been ascribed to a CD4+/CD8+ subpopulation of normal thymocytes. KKF's unique TCR structure may offer an explanation for the functional anomalies observed.

scholarly journals Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes.

1993 ◽  
Vol 178 (2) ◽  
pp. 615-622 ◽  
Author(s):  
H T Petrie ◽  
F Livak ◽  
D G Schatz ◽  
A Strasser ◽  
I N Crispe ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Model Systems ◽  
Allelic Exclusion ◽  
Alpha Chain ◽  
Enhanced Production ◽  
Germline Genes ◽  
Alpha Beta

Peripheral T lymphocytes each express surface T cell receptor (TCR) alpha and beta chains of a single specificity. These are produced after random somatic rearrangements in TCR alpha and beta germline genes. Published model systems using mice expressing TCR alpha and/or beta chain transgenes have shown that allelic exclusion occurs conventionally for TCR-beta. TCR alpha chain expression, however, appears to be less strictly regulated, as endogenous TCR alpha chains are often found in association with transgenic TCR beta chains in TCR alpha/beta transgenic mice. This finding, coupled with the unique structure of the TCR alpha locus, has led to the suggestion that unlike TCR beta and immunoglobulin heavy chain genes, TCR alpha genes may make multiple rearrangements on each chromosome. In the current study, we demonstrate that the majority of TCR-, noncycling thymocytes spontaneously acquire surface expression of CD3/TCR. Further, we show that cultured immature thymocytes originally expressing specific TCR alpha and beta chains may lose surface expression of the original TCR alpha, but not beta chains. These data provide evidence that not only must multiple rearrangements occur, but that TCR alpha gene rearrangement continues even after surface expression of a TCR alpha/beta heterodimer, apparently until the recombination process is halted by positive selection, or the cell dies. Sequential rearrangement of TCR alpha chain genes facilitates enhanced production of useful thymocytes, by increasing the frequency of production of both in-frame rearrangements and positively selectable TCR alpha/beta heterodimers.

scholarly journals Regions of the T cell receptor alpha and beta chains that are responsible for interactions with CD3.

1991 ◽  
Vol 173 (5) ◽  
pp. 1247-1256 ◽  
Author(s):  
L Tan ◽  
J Turner ◽  
A Weiss
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Activation ◽  
Cell Receptor ◽  
Surface Expression ◽  
Functional Coupling ◽  
Beta Chain ◽  
Alpha Beta ◽  
Chimeric Molecules ◽  
Stimulation Of

The T cell antigen receptor consists of the Ti alpha/beta heterodimer which recognizes antigen, and the associated CD3 chains, thought to be involved in signal transduction. To understand the nature of the interaction between Ti and CD3, chimeric molecules which included the COOH-terminal segments of Ti alpha or beta linked to the extracellular segment of CD8, were transfected into a mutant T cell deficient in Ti beta chain expression and cell surface CD3. Both chimeric chains were required to express the chimeric Ti and to restore CD3 surface expression. CD8/Ti and CD3 cointernalized and coimmunoprecipitated. Stimulation of the chimeric receptor induced transmembrane signaling events and cell activation. These results demonstrate that the Ti alpha and beta COOH termini containing the transmembrane domains are sufficient for structural and functional coupling of Ti to CD3.

scholarly journals Surface expression of only gamma delta and/or alpha beta T cell receptor heterodimers by cells with four (alpha, beta, gamma, delta) functional receptor chains.

1988 ◽  
Vol 168 (3) ◽  
pp. 1003-1020 ◽  
Author(s):  
T Saito ◽  
F Hochstenbach ◽  
S Marusic-Galesic ◽  
A M Kruisbeek ◽  
M Brenner ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Surface ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Surface Expression ◽  
Gamma Delta ◽  
Stringent Control ◽  
Repertoire Diversity ◽  
Alpha Beta ◽  
Functional Receptor

Surface expression of TCR dimers by cells synthesizing three or four distinct types of receptor chains was analyzed. Cells containing intact gamma, alpha, and beta chains had only gamma delta dimers on the cell surface. In human PEER cells, addition of a functional alpha chain led to the loss of gamma delta dimer expression and expression of only alpha beta dimers. This result was not due to transcriptional down-regulation of the gamma or delta loci. In murine cells expressing all four chains, both gamma delta and alpha beta dimers could be demonstrated on a single cell. No other chain combinations (alpha gamma, alpha delta, beta gamma, or beta delta) were detected. Thus, there is stringent control of assembly and/or transport of TCR heterodimers, such that functional receptors consist only of alpha beta and gamma delta pairs, and no additional repertoire diversity is generated by cross pairing.

Rearrangement of the T-cell receptor alpha, beta and gamma chain genes in chronic lymphocytic leukemia

1990 ◽  
Vol 14 (2) ◽  
pp. 131-137 ◽  
Author(s):  
Andras Perl ◽  
John P. Di Vincenzo ◽  
Daniel H. Ryan ◽  
Peter Gergely ◽  
Agnes Szigeti ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Gamma Chain ◽  
Receptor Alpha ◽  
Alpha Beta ◽  
Cell Receptor Alpha

scholarly journals Expression and rearrangement of the alpha, beta, and gamma chain genes of the T cell receptor in cloned murine large granular lymphocyte lines. No correlation with the cytotoxic spectrum.

1986 ◽  
Vol 164 (2) ◽  
pp. 428-442 ◽  
Author(s):  
K Ikuta ◽  
M Hattori ◽  
K Wake ◽  
S Kano ◽  
T Honjo ◽  
...  
Keyword(s):  
T Cell ◽  
Nk Cells ◽  
T Cell Receptor ◽  
Blot Hybridization ◽  
Cell Receptor ◽  
Chain Gene ◽  
Northern Blot Hybridization ◽  
Beta Chain ◽  
Gamma Chain ◽  
Alpha Beta

Using cloned murine large granular lymphocyte (LGL) lines, the expression and the rearrangement of the alpha, beta, and gamma chain genes of the T cell receptor (TCR) were analyzed. Morphological, phenotypical, as well as functional studies indicated that the LGL lines were identical to normal, endogenous NK cells. Northern blot hybridization analysis indicated that the full-length transcripts of all the alpha, beta, and gamma chain genes were expressed in most of the LGL lines, including two lines derived from athymic nude mice. In one line, SPB, however, no transcript of the gamma chain gene was detected, whereas the alpha and beta chain genes were clearly expressed. In every LGL line studied, all of the alpha, beta, and gamma chain genes were rearranged. Conforming to the results of Northern blot hybridization study, the gamma chain gene of the SPB line was aberrantly rearranged, whereas those of all the other lines were productively rearranged. The results clearly revealed that NK cells represented a population of lymphocytes genetically committed to the T cell lineage. It was also suggested that the expression and rearrangement of the TCR genes of NK cells might occur in a thymus-independent fashion. An SPB line without expression of the gamma chain gene could exhibit NK activity indistinguishable from other NK lines. Furthermore, the rearrangement patterns of the beta chain gene did not correlate with the specificity of the cytotoxic activity. These results strongly suggested that the cytotoxic activity in NK cells was not directly mediated by TCR on them. We particularly noted that the beta chain gene of most independently established LGL lines showed identical patterns of rearrangement, indicating that they used the same V beta and J beta gene segments. The significance of the restricted pattern of rearrangement of the beta chain gene in LGL lines, as well as the possible functional roles of TCR on NK cells, was discussed.

scholarly journals A unique V-J-C-rearranged gene encodes a gamma protein expressed on the majority of CD3+ T cell receptor-alpha/beta- circulating lymphocytes.

1988 ◽  
Vol 167 (2) ◽  
pp. 694-699 ◽  
Author(s):  
F Triebel ◽  
F Faure ◽  
M Graziani ◽  
S Jitsukawa ◽  
M P Lefranc ◽  
...  
Keyword(s):  
T Cell Receptor ◽  
Peripheral Blood ◽  
Antigenic Determinant ◽  
Cell Receptor ◽  
Gamma Chain ◽  
Gene Encoding ◽  
Circulating Lymphocytes ◽  
Alpha Beta ◽  
Human Pbls ◽  
Cell Receptor Alpha

We have recently described an mAb, anti-Ti gamma A, that recognizes an antigenic determinant carried by a TCR gamma chain. This antibody binds to approximately 3% of human PBLs and delineates a CD2+, CD3+, TCR-alpha/beta-, CD4-, CD8+/-, CD5+, NKH1-, and HLA class II- subset. The present study was designed to identify the gene encoding the Ti gamma A epitope. A first analysis was carried out on a previously characterized TCR gamma + fetal-cloned cell line termed F6C7. It was found that F6C7 cells have one gamma rearrangement on each chromosome: one joins V gamma 3 to J gamma 1, and the second joins V gamma 9 to J gamma P. Because only the latter allele appeared to be transcribed in the F6C7 lymphocytes, these data strongly suggested that anti-Ti gamma A mAb is specific for either a V gamma 9 or a V gamma 9-J gamma P-encoded peptide. To confirm this point, we studied an additional series of 13 randomly selected Ti gamma A+ cloned cells derived from peripheral blood of three distinct adult individuals. Each one of these lymphocytes was shown to both possess and transcribe a V gamma 9-J gamma P-C gamma 1-rearranged gene. It is therefore concluded that a predominant subpopulation of CD3+ TCR-alpha/beta- human circulating T lymphocytes (namely, the subset defined by anti-Ti gamma A mAb) surface expresses a gamma protein with a limited potential of variability from one cell to another.

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