Ludwig Institute for Cancer Research Limited

Immanuel F Luescher

Philippe Guillaume

Danijel Dojcinovic

Julien Schmidt

Pedro Romero

Jean-Charles Cerottini

Fabienee Anjuere

Andreas Layer

Some aspect of this disclosure provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized. The use of reversible MHC multimers as provided herein, accordingly, allows for the detection and isolation of bona fide antigen-specific CD8+ T cells without inducing activation dependent cell death, including rare, therapeutically valuable T-cells expressing T-cell receptors binding tumor antigens with high affinity. Methods for the production and use of reversible multimers are also provided.

Reversible protein multimers, methods for their production and use

Some aspects of this invention are based on the recognition that reversible protein multimers in which monomeric proteins are conjugated to a carrier molecule via chelation complex bonds are stable under physiological conditions and can be dissociated in a controlled manner under physiological, nontoxic conditions. Accordingly, such protein multimers are useful for a variety of in vitro, ex vivo, and in vivo application for research, diagnostics, and therapy. Some aspect of this invention provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized. The use of reversible MHC multimers as provided herein, accordingly, allows for the detection and isolation of bona fide antigen-specific CD8+ T cells without inducing activation dependent cell death, including rare, therapeutically valuable T-cells expressing T-cell receptors binding tumor antigens with high affinity. Methods for the production and use of reversible multimers are also provided.

The invention relates to methods for making synthetic, photoreactive peptides and their use. A photoreactively labelled amino acid is incorporated into the peptide. The resulting peptide, when compared to the non-labelled form, is not impaired with respect to its ability to bind an MHC molecule.

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Gollion, Switzerland

Immanuel F Luescher