The aim of this thesis was to explore the link between stability and immunogenicity of therapeutic proteins. Using various environmental stress conditions, protein aggregates were formed, biophysically characterized, and the relationship between the degree of aggregation and the impact on the protein bioactivity highlighted. Then, in view of simulating in vitro the phenomena of in situ protein aggregation once injected in the subcutaneous tissue, we reviewed the literature on 2D and 3D assays predicting the potential immunogenicity of (new candidate) therapeutic proteins. Based on that, an immunocompetent model of the human subcutaneous tissue was developed, combining hydrogels scaffolds into which antigen-presenting cells (MUTZ-3 dendritic cells) were embedded.