I'm wondering if there is some threshold in size or a specific structural property that determines if a small protein or large peptide would cause an immune reaction.
Context: there are a number of drugs being developed based on antibody mimetics (small protein scaffolds with stable folding). These tend to have a size around 50-60 aminoacids (6-7 kD). These tend to be much easier to design than human / humanized antibodies. However, it is not uncommon for these to cause anaphylaxis, especially if administered repeatedly. It may be good to somehow design a version of a small antibody mimetic which itself does not cause an immune reaction.
Are peptides around 10-20 aminoacids typically immunogenic? What about slightly larger ones up to 30 aminoacids? Does it matter if they have a stable secondary or tertiary structure?