scholarly journals Expression of two alpha chains on the surface of T cells in T cell receptor transgenic mice.

1993 ◽  
Vol 178 (5) ◽  
pp. 1807-1811 ◽  
Author(s):  
W R Heath ◽  
J F Miller
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Flow Cytometric Analysis ◽  
Cell Receptor ◽  
Specific Monoclonal Antibody ◽  
Beta Chain ◽  
Flow Cytometric

CD8+ T cells taken directly from mice expressing a Kb-specific T cell receptor (TCR) transgene expressed the transgenic TCR in a bimodal profile as detected by flow cytometric analysis using a clonotype-specific monoclonal antibody. Those cells expressing the lower density of the transgenic TCR expressed the transgenic beta chain and two different alpha chains on their surface. One alpha chain was the product of the alpha transgene, whereas the other was derived by endogenous rearrangement. This report provides the first demonstration that T cells isolated directly from mice may express two different TCR clonotypes on their surface. The potential consequences of this finding for studies using TCR transgenic mice and for the induction of autoimmunity are discussed.

scholarly journals Premature Expression of T Cell Receptor (Tcr)αβ Suppresses Tcrγδ Gene Rearrangement but Permits Development of γδ Lineage T Cells

2000 ◽  
Vol 192 (4) ◽  
pp. 537-548 ◽  
Author(s):  
Kathleen Terrence ◽  
Christian P. Pavlovich ◽  
Errin O. Matechak ◽  
B.J. Fowlkes
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Gene Rearrangement ◽  
T Cell Development ◽  
Cell Receptor ◽  
Lineage Commitment ◽  
Cd8 Cells

The T cell receptor (TCR)γδ and the pre-TCR promote survival and maturation of early thymocyte precursors. Whether these receptors also influence γδ versus αβ lineage determination is less clear. We show here that TCRγδ gene rearrangements are suppressed in TCRαβ transgenic mice when the TCRαβ is expressed early in T cell development. This situation offers the opportunity to examine the outcome of γδ versus αβ T lineage commitment when only the TCRαβ is expressed. We find that precursor thymocytes expressing TCRαβ not only mature in the αβ pathway as expected, but also as CD4−CD8− T cells with properties of γδ lineage cells. In TCRαβ transgenic mice, in which the transgenic receptor is expressed relatively late, TCRγδ rearrangements occur normally such that TCRαβ+CD4−CD8− cells co-express TCRγδ. The results support the notion that TCRαβ can substitute for TCRγδ to permit a γδ lineage choice and maturation in the γδ lineage. The findings could fit a model in which lineage commitment is determined before or independent of TCR gene rearrangement. However, these results could be compatible with a model in which distinct signals bias lineage choice and these signaling differences are not absolute or intrinsic to the specific TCR structure.

scholarly journals T cell receptor ligation induces interleukin (IL) 2R beta chain expression in rat CD4,8 double positive thymocytes, initiating an IL-2-dependent differentiation pathway of CD8 alpha+/beta- T cells.

1993 ◽  
Vol 177 (2) ◽  
pp. 541-546 ◽  
Author(s):  
J H Park ◽  
R Mitnacht ◽  
N Torres-Nagel ◽  
T Hünig
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Cell Receptor ◽  
Beta Chain ◽  
Double Positive ◽  
Alpha Chain ◽  
Alpha Beta

The role of interleukin (IL)2 in intrathymic T cell development is highly controversial, and nothing is known about IL-2R expression on thymocytes of the T cell receptor (TCR) alpha/beta lineage undergoing TCR-driven differentiation events. We analyze here IL-2R alpha and beta mRNA expression in an in vitro system where newly generated rat CD4,8 double positive (DP) thymocytes respond to TCR ligation plus IL-2 (but not to either stimulus alone) with rapid differentiation to functional CD8 single positive T cells (Hünig, T., and R. Mitnacht. 1991. J. Exp. Med. 173:561). TCR ligation induced expression of IL-2R beta (but not alpha) chain mRNA in DP thymocytes. Addition of IL-2 then lead to functional maturation and expression of the IL-2R alpha chain. To investigate if the CD8 T cells generated via this IL-2R beta-driven pathway in vitro correspond to the bulk of CD8 T cells seeding peripheral lymphoid organs in vivo, we compared their phenotype to that of lymph node CD8 T cells. Surprisingly, analysis of CD8 cell surface expression using a novel anti-CD8 monoclonal antibody specific for the alpha/beta heterodimeric isoform, and of CD8 alpha and beta chain mRNA revealed that T cells generated by TCR ligation plus IL-2 resemble thymus-independent rather than thymus-derived CD8 cells in that they express CD8 alpha without beta chains. These findings demonstrate that TCR crosslinking induces functional IL-2R on immature DP rat thymocytes. In addition, they show that at least in vitro, CD8 alpha/alpha T cells are generated from TCR-stimulated DP thymocytes (which express the CD8 alpha/beta in the heterodimeric isoform) along an IL-2-driven pathway of T cell differentiation.

scholarly journals Normal T lymphocytes can express two different T cell receptor beta chains: implications for the mechanism of allelic exclusion.

1995 ◽  
Vol 181 (4) ◽  
pp. 1587-1591 ◽  
Author(s):  
E Padovan ◽  
C Giachino ◽  
M Cella ◽  
S Valitutti ◽  
O Acuto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Human Peripheral Blood ◽  
Flow Cytometric Analysis ◽  
Cell Receptor ◽  
Allelic Exclusion ◽  
Flow Cytometric ◽  
T Cell Receptor Beta

We have examined the extent of allelic exclusion at the T cell receptor (TCR) beta locus using monoclonal antibodies specific for V beta products. A small proportion (approximately 1%) of human peripheral blood T cells express two V beta as determined by flow cytometric analysis, isolation of representative clones, and sequencing of the corresponding V beta chains. Dual beta T cells are present in both the CD45R0+ and CD45R0- subset. These results indicate that dual beta expression is compatible with both central and peripheral selection. They also suggest that the substantial degree of TCR beta allelic exclusion is dependent only on asynchronous rearrangements at the beta locus, whereas the role of the pre-TCR is limited to signaling the presence of at least one functional beta protein.

Self-reactive memory-phenotype CD8 T cells exhibit both MHC-restricted and non-MHC-restricted cytotoxicity: a role for the T-cell receptor and natural killer cell receptors

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2116-2123 ◽  
Author(s):  
Salim Dhanji ◽  
Soo-Jeet Teh ◽  
Darryl Oble ◽  
John J. Priatel ◽  
Hung-Sia Teh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cd8 T Cells ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Target Cells ◽  
Lymphoid Tissues

Abstract We have recently shown that interleukin-2 (IL-2)-activated CD8+CD44hi cells from normal mice express both adaptive and innate immune system receptors and specifically kill syngeneic tumor cells, particularly those that express NKG2D ligands. Here we show that CD8+ T cells from antigen-expressing H-Y T-cell receptor (TCR) transgenic mice also exhibit characteristics of both T cells and natural killer (NK) cells. Interaction with cognate self-antigen was required for the optimal expansion of these cells in peripheral lymphoid tissues. Although these cells possess a higher activation threshold relative to naive T cells, they can be activated by cytokine alone in vitro. They also undergo bystander proliferation in response to a bacterial infection in vivo. Interestingly, upon activation, the cells express the NKG2D receptor as well as the DNAX activation protein 12 (DAP12) adaptor protein. We provide evidence that NKG2D can act additively with the TCR in the killing of target cells, and it can also function as a directly activating receptor in non-major histocompatibility complex (MHC)-restricted killing of target cells. These properties of CD8+ T cells from H-Y TCR transgenic mice are remarkably similar to CD8+CD44hi cells that are found in normal mice. The H-Y TCR transgenic mice provide a well-defined system for characterizing the developmental biology and function of these cells. (Blood. 2004;104:2116-2123)

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