Polymyositis, Topological Proteomics Technology and Paradigm for Cell Invasion Dynamics

Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. This investigation presents a technology for the direct mapping of protein networks involved in T-cell invasion in situ. Simultaneous localization of 17 adhesive cell surface receptors reveals 18 different combinatorial expression patterns (CEP), which are unique for the T-cell invasion process in muscle tissue. Each invasion step can be assigned to specific CEP on the surface of individual T-cells. This indicates, that the T-cell invasion is enciphered combinatorially in the T-cells' adhesive cell surface proteome fraction. Given 217 possible combinations, the T-cell appears to have at its disposal a highly non-random restricted repertoire to specify migratory pathways at the cell surface. These higher-level order functions in the cellular proteome cannot be detected by large-scale protein profiling techniques from tissue homogenates. High-throughput whole cell mapping machines working on structurally intact tissues, as shown here, will allow to measure how cells of different origin (immune cells, tumor cells) combine cell surface receptors to encipher specificity and selectivity for interactions.