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Günter Hämmerling

Publications and source records attributed to Günter Hämmerling.

4 recordsLinked to original sources
PubMed2006

Interaction of ERp57 and tapasin in the generation of MHC class I-peptide complexes.

Antigen presentation by MHC class I molecules is necessary for CD8 T-cell activation. Optimal peptide loading onto MHC class I molecules occurs mainly in the peptide-loading complex in the endoplasmic reticulum. The identification of a covalent association between the thiol oxidoreductase ERp57 and tapasin, and its impact on the loading complex, are important recent developments in this field of research. In the absence of ERp57, the recruitment of MHC class I molecules into this complex by tapasin is greatly impaired both in the number of molecules and in their interaction time, suggesting a key structural role for the ERp57-tapasin association in the peptide-loading complex. The role of ERp57 as a thiol oxidoreductase in the peptide-loading complex remains, however, controversial and further research regarding this subject is required.

Animals↗
PubMed2006

Cross-presentation of antigens from apoptotic tumor cells by liver sinusoidal endothelial cells leads to tumor-specific CD8+ T cell tolerance.

Development of tumor-specific T cell tolerance contributes to the failure of the immune system to eliminate tumor cells. Here we report that hematogenous dissemination of tumor cells followed by their elimination and local removal of apoptotic tumor cells in the liver leads to subsequent development of T cell tolerance towards antigens associated with apoptotic tumor cells. We provide evidence that liver sinusoidal endothelial cells (LSEC) remove apoptotic cell fragments generated by induction of tumor cell apoptosis through hepatic NK1.1+ cells. Antigen associated with apoptotic cell material is processed and cross-presented by LSEC to CD8+ T cells, leading to induction of CD8+ T cell tolerance. Adoptive transfer of LSEC isolated from mice challenged previously with tumor cells promotes development of CD8+ T cell tolerance towards tumor-associated antigen in vivo. Our results indicate that hematogenous dissemination of tumor cells, followed by hepatic tumor cell elimination and local cross-presentation of apoptotic tumor cells by LSEC and subsequent CD8+ T cell tolerance induction, represents a novel mechanism operative in tumor immune escape.

Adoptive Transfer↗
PubMed2002

Temporal Cre-mediated recombination exclusively in endothelial cells using Tie2 regulatory elements.

SUMMARY: The versatility of the bacteriophage Cre/LoxP system is dependent on the availability of a spectrum of tissue-specific Cre transgenic mice to address a host of biological questions. In this paper, we report on the generation of an inducible Tie2Cre transgenic mouse line that facilitates gene targeting exclusively in endothelial cells. The temporal manner of recombination is feasible through the use of a Cre-estrogen receptor fusion protein ER(T2) and was, in practical terms, achieved by feeding the animals the estrogen antagonist tamoxifen orally for 5 weeks. High efficiency of recombination was found in the vast majority of endothelial cell populations examined, as monitored by an EGFP reporter mouse line. Critically, no EGFP expression was observed in any uninduced mice. This inducible Cre line will be a very beneficial asset to investigating the role of endothelial specific genes in the adult mouse and to induce transgenes in the endothelium in an extremely efficient manner. genesis 33:191-197, 2002.

Animals↗