CBy.Cg-Thy1^a Tg(TcraCl1,TcrbCl1)1Shrm/J

Stock number: 005922
Strain synonyms: BALB/c ByJ Cl.1 Thy1.1, BALB/c clone 1 Thy1.1
Research areas: Cancer Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Clone-1 TCR (also called Clone 1 Thy1.1 TCR or Cl.1 TCR) transgenic mice were designed to optimize conditions for tumor eradication by low avidity tumor-specific T cells and may also be useful in general studies of T cell avidity, tolerance, positive/negative selection, and activation.

Detailed description

Male mice that are hemizygous for the Clone-1 TCR (also called Clone 1 Thy1.1 TCR or Cl.1 TCR) transgene are viable, fertile, and normal in size. Females are very weak and have low fecundity. The donating investigator reports that all transgenic mice are prone to tumor development by 5-6 months of age. The transgene encodes a rearranged low avidity T cell receptor that recognizes an influenza virus hemagglutinin epitope (HA_518-526) restricted by MHC class I H-2K^d. The phenotype below is as defined by the B10.D2 background (see Stock No. 005895). Flow cytometric analysis shows appropriate skewing towards the CD8⁺ T cell compartment in thymocytes and peripheral lymphocytes. CD8⁺ T cells can be induced to exhibit both effector function and antitumor activity. This mouse is further modified with the Thy1^a allele, rather than the alternate allele present in C57BL/10, DBA/2, and BALB/c mice. Thus, cell populations derived from these transgenic mice can be distinguished from syngeneic host and other mice with the alternate allele via flow cytometry. These Clone-1 TCR (also called Clone 1 Thy1.1 TCR or Cl.1 TCR) transgenic mice were designed to optimize conditions for tumor eradication by low avidity tumor-specific T cells and may also be useful in general studies of T cell avidity, tolerance, positive/negative selection, and activation.

Of note, Clone-1 TCR mice are also available on a C57BL/10 congenic background (see Stock No. 005895).

In an attempt to offer alleles on well-characterized or multiplegenetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A low avidity influenza hemagglutinin (HA)-specific CD8⁺ T cell clone (Clone 1) was expanded from the tolerant repertoire of a transgenic mouse expressing HA as a self-antigen on insulin-producing beta cells of the pancreatic islets (InsHA mouse). This T cell receptor sequence, specific for influenza virus HA_518-526 epitope restricted by MHC class I H-2K^d, was cloned into Tcra-V1,Tcra-J(J11) and Tcrb-V8.2,Tcrb-D,Tcrb-J (J2.4) expression vectors. The facility generating this mutant used "B10D2/nSnJ" mice derived from Stock No. 000463 as founder stock. The constructs were co-injected into fertilized B10D2/nSnJ eggs. Transgenic mice were bred to B10D2/nSnJ mice for 8 generations. Thereafter, transgenic mice were bred to B10D2/nSnJ mice homozygous for the Thy1^a allele (coding for the Thy1.1 leukocyte alloantigen) to generate transgenic mice homozygous for Thy1^a. After this, mutant mice were backcrossed to BALB/cByJ for 13 generations resulting in Clone 1 transgenic mice homozygous for the BALB/c-derived Thy1^b (coding for the Thy1.2 leukocyte alloantigen). Upon arrival at The Jackson Laboratory, transgenic Thy1^b/b males were bred with Stock No. 005443 (BALB/cByJ backcrossed mice homozygous for Thy1^a) or wildtype Thy1^a/a sibling females to generate Clone 1 transgenic Thy1^a/a mice.

Allele

Symbol: Tg(TcraCl1,TcrbCl1)1Shrm
Name: transgene insertion 1, Linda Sherman
MGI accession ID: MGI:3617607
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(TcraCl1,TcrbCl1)1Shrm
Marker name: transgene insertion 1, Linda Sherman
Chromosome: UN
Strain of origin: B10.D2-Hc¹ H2^d H2-T18^c/nSnJ
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Molecular note: The transgene encodes a low avidity T cell receptor (TCR) that recognizes the influenza virus hemagglutinin (HA) epitope HA518-526 in the context of the H2-K^d MHC class I molecule. The rearranged Tcra and Tcrb genes, which have joined Valpha1/Jalpha11 and Vbeta8.2/D/Jbeta2.4, respectively, were amplified from cytotoxic T lymphocyte (CTL) clone 1. Clone 1 was derived from a transgenic B10.D2 mouse that expressed influenza virus HA as a self-antigen in pancreatic beta cells, which resulted in production of lower-avidity TCRs than those made by wild-type B10.D2 mice after infection with influenza virus strain A/PR/8/32.
General note: CD8⁺ T cells bearing this transgene, when transferred to mice that develop pancreatic tumors expressing influenza virus HA, can be induced to exhibit both effector function and antitumor activity only if HA-responsive CD4⁺ T cells are co-transferred and the mice are subsequently infected with influenza virus. : J:97745

Allele

Symbol: Thy1^a
Name: a variant
MGI accession ID: MGI:3579311
Generation method: Not Applicable
Marker symbol: Thy1
Marker name: thymus cell antigen 1, theta
Chromosome: 9
Strain of origin: Not Applicable
Site of expression: The Thy1 locus determines a surface antigen present on cells of the thymus, a number of mouse leukemias, brain, and in lesser amounts on lymph node and spleen cells.
Molecular note: The allele Thy1^a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains.
General note:

The Thy1 locus determines a surface antigen present on cells of the thymus, a number of mouse leukemias, brain, and in lesser amounts on lymph node and spleen cells. The allele Thy1^a determines an antigenic specificity, Thy-1.1, found in the AKR and RF strains; the allele Thy1^b determines an antigenic specificity, Thy-1.2, found in the C3HeB/Fe and many other strains (J:5243, J:5012, J:4469). The Thy1 antigen is probably present on all T lymphocytes and absent from all B lymphocytes, and it thus serves as a valuable T-cell marker (J:5243). It is very widely used in experiments designed to determine the distribution and function of T-cells. Thy1 specifies a T-cell surface glycoprotein, T25, with a molecular weight of 25 kDa (J:5707). The protein appears to be anchored in the cell membrane by a lipid that is either phosphotidylinositol or closely related to it (J:12016). Thy1 may function in the cell membrane as a signal transduction molecule (J:8333). The Thy1 locus, or possibly a gene closely linked to it, controls quantitative expression of a protein that is the same size as Thy1 and is expressed on thymus and brain but not on lymph node and spleen cells (J:7900).