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Welcome to the Antigen Presentation Group

Kajsa Paulsson,  PhD, Group Leader  Phone: +46 706 08 33 181 E-mail: Kajsa_M.Paulsson@med.lu.se

Our projects address extremely important scientific questions with a significant potential for practical applications. Understanding which peptides leads to tapasin release and subsequent cell surface presentation should aid the future design of vaccines and immunotherapy.

MHC class I molecules plays a key role in the immune recognition of intracellular pathogens e.g. virus and cancer. Their function is to provide cytotoxic T cells with information on the intracellular protein content of target cells; sampling peptides derived from cytosolic proteins and presenting them at the cell surface.

There is, however, an inherent problem in the transition from a sampling mode, where a large peptide pool is considered, to a presentation mode, where the MHC class I has committed itself to one peptide: during sampling, the available peptide pool is heavily skewed towards unstable binders, whereas during presentation, the peptides must remain stably associated. Without some editing, or quality control, mechanism during peptide loading, most MHC class I molecules would sample peptides unfit for presentation. In the ER, an entire multi-chaperone peptide loading complex has been devoted to the formation of stable peptide-MHC class I complexes.

One of these chaperones, tapasin, plays a crucial role in stabilizing the complex, facilitating and editing peptide binding, and retaining MHC-I until an appropriate peptide has been bound. However, the all-important criteria for tapasin release of MHC class I remain elusive. Our recent data suggest that tapasin is responsible for the final control of peptide-MHC-I-maturation in a process involving not only affinity and stability, but also structural, parameters.

We are currently using structural, biochemical and bioinformatics tools to examine in detail how tapasin affects peptide-MHC class I interaction, how tapasin itself interacts with peptide-MHC class I complexes, and what the rules of tapasin-MHC class I release are.