Naslov
A "Switch-on" T Cell Receptor for the Investigation of Thymic Development

Autori
Hemmer, S. ; Polić, Bojan ; Wunderlich, F.T. ; Rajewsky, K. ; Waisman, A. ; Buch, T.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
1st Joint Meeting of European National Societies of Immunology : 16th European Congress of Immunology / Bernard, Alain ; Kaufmann, Stefan H.E. - Pariz : EFIS, 2006, 284-284

Skup
1st Joint Meeting of European National Societies of Immunology - 16th European Congress of Immunology

Mjesto i datum
Pariz, Francuska, 06.09.2006. - 09.09.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
T cell receptor ; thymic development ; positive and negative selection of T cell precursors

Sažetak
Positive and negative selection of T cell precursor expressing a T cell receptor (TCR) of unknown specificity ensures that only such cells are released to the periphery that expresses a selfrestricted TCR without autoreactive specificity. Although it is of fundamental importance for the understanding of T cell differentiation and tolerance induction, only little is known about the process which allows T cell precursors to distinguish between autoreactive specificities (high avidity to self_MHC/peptide) and self-restricted specificities (intermediate avidity). To investigate this process we developed a novel mouse model that allows us to induce the expression of a defined TCR in thymocytes. The wave of cells caring the same specificity is either positively or negatively selected, dependent on the respective thymic environment. We want to use this wave to investigate in more detail the signal transduction and gene activation pathways that are involved in the thymic selection processes. To this end we have generated by gene targeting an allele of the TCRa locus which carries the VaJa exon of the HY-TCR opposite to the transcriptional direction. By use of two antidromic loxP sites this exon can be inverted and thus expression of the HY-TCR (in conjunction with the conventional transgene for the HYb chain) is made possible. To exclude the generation of other TCR a large Cre-mediated recombination event removed the TCRd locus as well as all Ja elements. Expression of the HY-TCRa chain from this modified TCRa allele was confirmed by flow cytometry. To restrict Cre-mediated inversion of the ‘ HYa-switch-on’ allele to the CD4CD8 positive compartment of T cell development we also generated an allele of the CD4 locus which expresses an estrogen receptor Cre fusion protein (CreERT2) that allows induction of Cre activity by injection of tamoxifen.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA