Tissue-invasive T cells are observed in many inflammatory dermatological diseases, but in most cases, it is not known how they were attracted, what they might recognize, and to which extent they are activated. Answering these questions is surely essential for understanding pathogeneses of the diseases. In a recent issue of Experimental Dermatology, Smith et al. showed that early signalling events in skin-resident T cells may be investigated by multiplex immunoprecipitation flow cytometry, even if only few T cells are available from skin biopsy samples. This new technology will most likely contribute to elucidating the role of skin-invasive T cells and to understanding the pathology of dermatological diseases.