scholarly journals Positive and Negative Selection in Transgenic Mice Expressing a T-Cell Receptor Specific for Influenza Nucleoprotein and Endogenous Superantigen

1993 ◽  
Vol 3 (3) ◽  
pp. 159-174 ◽  
Author(s):  
Clio Mamalaki ◽  
James Elliott ◽  
Trisha Norton ◽  
Nicholas Yannoutsos ◽  
Alain R. Townsend ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class Ii ◽  
Cytotoxic T Cell ◽  
Dependent Manner ◽  
Class Ii Mhc ◽  
Peripheral T Cells

A transgenic mouse was generated expressing on most (>80%) of thymocytes and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5). This clone is CD8+and recognizes αα366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class ,MHC Db(Townsend et al., 1986). The receptor utilizes the Vβ11 and Vα4 gene segments for the β chain and α chain, respectively (Palmer et al., 1989). The usage of Vβ11 makes this TcR reactive to Class II IE molecules and an endogenous ligand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the development of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MHC IE (e.g., CBA/Ca H-2kand BALB/c H-2d) and the endogenous Mtv ligands. Positive selection of CD8+T cells expressing the Vβ11 is seen in C57BL/10 transgenic mice (H-2b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner after a period ofin vitroculture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-positive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8+peripheral T-cells in these (H-2kor H-2d) F5 mice are predominantly Vβ11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even following backcrossing of the F5 TcR transgene to H-2dscid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chain genes is impaired.

scholarly journals Characterization of human T cells reactive with the Mycoplasma arthritidis-derived superantigen (MAM): generation of a monoclonal antibody against V beta 17, the T cell receptor gene product expressed by a large fraction of MAM-reactive human T cells.

1991 ◽  
Vol 174 (4) ◽  
pp. 891-900 ◽  
Author(s):  
S M Friedman ◽  
M K Crow ◽  
J R Tumang ◽  
M Tumang ◽  
Y Q Xu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Activity ◽  
Cell Receptor ◽  
Cytotoxic T Cell ◽  
Mycoplasma Arthritidis ◽  
Human T Cells

While all known microbial superantigens are mitogenic for human peripheral blood lymphocytes (PBL), the functional response induced by Mycoplasma arthritidis-derived superantigen (MAM) is unique in that MAM stimulation of PBL consistently results in T cell-dependent B cell activation characterized by polyclonal IgM and IgG production. These immunostimulatory effects of MAM on the humoral arm of the human immune system warranted a more precise characterization of MAM-reactive human T cells. Using an uncloned MAM reactive human T cell line as immunogen, we have generated a monoclonal antibody (mAb) (termed C1) specific for the T cell receptor V beta gene expressed by the major fraction of MAM-reactive human T cells, V beta 17. In addition, a V beta 17- MAM-reactive T cell population exists, assessed by MAM, induced T cell proliferation and cytotoxic T cell activity. mAb C1 will be useful in characterizing the functional properties of V beta 17+ T cells and their potential role in autoimmune disease.

scholarly journals CD4+ T Cells from Glutamic Acid Decarboxylase (GAD)65-specific T Cell Receptor Transgenic Mice Are Not Diabetogenic and Can Delay Diabetes Transfer

2002 ◽  
Vol 196 (4) ◽  
pp. 481-492 ◽  
Author(s):  
Kristin V. Tarbell ◽  
Mark Lee ◽  
Erik Ranheim ◽  
Cheng Chi Chao ◽  
Maija Sanna ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Glutamic Acid Decarboxylase ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Acid Decarboxylase ◽  
Gad 65

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes. We have generated transgenic mice on the NOD background expressing a T cell receptor (TCR)-specific for peptide epitope 286–300 (p286) of GAD65. These mice have GAD65-specific CD4+ T cells, as shown by staining with an I-Ag7(p286) tetramer reagent. Lymphocytes from these TCR transgenic mice proliferate and make interferon γ, interleukin (IL)-2, tumor necrosis factor (TNF)-α, and IL-10 when stimulated in vitro with GAD65 peptide 286–300, yet these TCR transgenic animals do not spontaneously develop diabetes, and insulitis is virtually undetectable. Furthermore, in vitro activated CD4 T cells from GAD 286 TCR transgenic mice express higher levels of CTL-associated antigen (CTLA)-4 than nontransgenic littermates. CD4+ T cells, or p286-tetramer+CD4+ Tcells, from GAD65 286–300-specific TCR transgenic mice delay diabetes induced in NOD.scid mice by diabetic NOD spleen cells. This data suggests that GAD65 peptide 286–300-specific T cells have disease protective capacity and are not pathogenic.

scholarly journals Functional differentiation of T cells in the intestine of T cell receptor transgenic mice

1997 ◽  
Vol 94 (8) ◽  
pp. 3920-3925 ◽  
Author(s):  
S. D. Hurst ◽  
S. M. Sitterding ◽  
S. Ji ◽  
T. A. Barrett
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Functional Differentiation

Naive T cells can mediate delayed-type hypersensitivity response in T cell receptor transgenic mice

1994 ◽  
Vol 24 (7) ◽  
pp. 1512-1516 ◽  
Author(s):  
Takehito Sato ◽  
Takeshi Sasahara ◽  
Yukitsugu Nakamura ◽  
Takako Osaki ◽  
Takanori Hasegawa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Delayed Type Hypersensitivity ◽  
Hypersensitivity Response ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Delayed Type Hypersensitivity Response

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 Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules.

1989 ◽  
Vol 169 (3) ◽  
pp. 795-806 ◽  
Author(s):  
H S Teh ◽  
H Kishi ◽  
B Scott ◽  
H Von Boehmer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Large Fraction ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Male Transgenic Mouse ◽  
Low Levels ◽  
High Level

Transgenic mice that carry on a large fraction of their T cells an alpha/beta T cell receptor that recognizes the male antigen in the context of H-2Db molecules were constructed. An mAb specific for the transgenic receptor was developed and used to analyze T cell subsets in male transgenic H-2b mice. The vast majority of immature CD4+8+ T cells that express the transgenic TCR were deleted in the male transgenic mouse. Nevertheless, the majority of T cells spared by this deletion process expressed a high level of the transgenic TCR. These T cells, however, had an abnormal CD4/CD8 phenotype in that they expressed either no CD8 molecules or only low levels.

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