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P 27 - Prof. Dr. Thomas Boehm

Molecular basis of antigen recognition by variable lymphocyte receptors (VLRs)


Prof. Dr. Thomas Boehm

MPI für Immunbiologie und Epigenetik, Freiburg

Stübeweg 51, 79108 Freiburg

Phone: +49 761 5108--328

Fax: + 49 761 5108-799





Project Summary



All multicellular organisms protect themselves against pathogens using sophisticated immune defenses. Recently, an alternative adaptive immune system was discovered in lamprey, which furnishes developing T- and B-like cells with somatically diversifying so-called variable lymphocyte receptors (VLRs). VLRs consist of repetitive arrays of leucine-rich repeat (LRR) modules, akin to other immune-related receptors. Lamprey T cells develop in the thymoid - the equivalent of the thymus in jawed vertebrates - and give rise to two different lineages expressing either VLRA or VLRC receptors. Our recent work provided evidence for selection of functional VLRC receptors with respect to the number of LRR modules in VLRC molecules and the sequence diversity of the N-terminal LRR1 domain. These findings impose significant constraints on the structure of presumptive interaction partners associated with signaling and sequence-specific repertoire formation. In the first half of the funding period, we propose to carry out a biochemical and functional characterization of candidate polymorphic interaction molecules of VLRC antigen receptors and to isolate the components of the VLRC signaling complex. In the second part of the funding period, the main focus ofthe work will be on the structural characterization of the VLRC antigen receptor with its interaction partners, with particular reference to the biochemical characterization of the dynamics of these complexes. We expect our analysis to contribute to a better understanding of the molecular architecture of antigen receptors in an alternative adaptive immune system.


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