| Summary: | The main food-origin antigens that the infant’s body is in contact with are cow’s milk proteins (CMP). Still, CMP are one of the main sources of beneficial biologically active peptides that play a role in treatment of non-communicable diseases. Safe methods to quickly predict the sensitizing potential of food proteins among their range of health-promoting properties are essential. The aim of study was to adapt an integrated approach combining several <i>in silico</i> (<i>IS</i>) studies and <i>in vitro</i> (<i>IV</i>) assays to screen the multifunctionality of CMP-derived peptides. Major histocompatability complex type II MHC II-binders, interleukin-4 and -10 inducers, interferon γ -inducers and immunobioactivity tools were used to predict the peptide-power of inducing allergies or tolerance. A comparison of the peptide profiless revealed the presence of one identical and one overlapping sequence in <i>IS</i> and <i>IV</i> hydrolysate. By <i>IS</i> analysis, four of 24 peptides were found to have high affinity and stimulate IL-4 expression, and by <i>IV,</i> one of seven peptides had this potential (Bos d9 peptide DIPNPIGSENSEK (195–208)). Three <i>IV</i> peptides may induce IL-10 expression. The <i>IV</i>/<i>IS</i> assessment seems promising agents for peptides’ potential determination dedicated only to preliminary screening of peptides. The <i>IV</i> verification is still crucial in further steps of studies.
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