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Development of innovative immunotherapeutic drugs

Reference number
IMF11-0090
Start and end dates
110701-130630
Amount granted
90 000 SEK
Administrative organization
Karolinska Institutet
Research area
Life Sciences

Summary

Cellular interactions between immune effector cells rely on ligand/receptor interactions. We will determine the three-dimensional crystal structure of the LLT1/CD161 complexe, whose interaction inhibits natural killer cell function and co-stimulates T cells. Structural information as well as biochemical and biophysical data gathered will greatly enhance our understanding of the role played by this fundamental interaction in immunity. Functional studies will be performed to verify structural findings and to test the effects of mutations on LLT1 and CD161. The soluble proteins generated will also be used to develop novel antibodies, screened for high affinity, blocking or triggering properties. The determination of the 3D structure of LLT1/CD161 complex will therefore allow the design of innovative drugs that could block/modulate immune responses in which LLT1/CD161 interaction is critical, like cancer, inflammation and infectious diseases. All the structural and functional information gathered within this research program will complete the conceptual framework on which to build up our understanding of the mechanisms that control the function of the cellular immune response. Ultimately, a detailed knowledge of these mechanisms should allow us to manipulate them to maximum effect in the design of novel immunotherapies.

Popular science description

Cellular interactions between immune effector cells rely on ligand/receptor interactions. We will determine the three-dimensional crystal structure of the LLT1/CD161 complexe, whose interaction inhibits natural killer cell function and co-stimulates T cells. Structural information as well as biochemical and biophysical data gathered will greatly enhance our understanding of the role played by this fundamental interaction in immunity. Functional studies will be performed to verify structural findings and to test the effects of mutations on LLT1 and CD161. The soluble proteins generated will also be used to develop novel antibodies, screened for high affinity, blocking or triggering properties. The determination of the 3D structure of LLT1/CD161 complex will therefore allow the design of innovative drugs that could block/modulate immune responses in which LLT1/CD161 interaction is critical, like cancer, inflammation and infectious diseases. All the structural and functional information gathered within this research program will complete the conceptual framework on which to build up our understanding of the mechanisms that control the function of the cellular immune response. Ultimately, a detailed knowledge of these mechanisms should allow us to manipulate them to maximum effect in the design of novel immunotherapies.