World Allergy Organization Journal 15(9) (2022) The immunopathogenesis of cow's milk protein allergy (CMPA) is based on different mechanisms related to immune recognition of protein epitopes, which are affected by industrial processing.The purpose of this WAO DRACMA paper is to: (i) give a comprehensive overview of milk protein allergens, (ii) to review their immunogenicity and allergenicity in the context of industrial processing, and (iii) to review the milk-related immune mechanisms triggering IgE-mediated immediate type hypersensitivity reactions, mixed reactions and non-IgE mediated hypersensitivities.The main cow's milk allergens - α-lactalbumin, β-lactoglobulin, serum albumin, caseins, bovine serum albumins, and others - may determine allergic reactions through a range of mechanisms. All marketed milk and milk products have undergone industrial processing that involves heating, filtration, and defatting. Milk processing results in structural changes of immunomodulatory proteins, leads to a loss of lipophilic compounds in the matrix, and hence to a higher allergenicity of industrially processed milk products. Thereby, the tolerogenic capacity of raw farm milk, associated with the whey proteins α-lactalbumin and β-lactoglobulin and their lipophilic ligands, is lost.The spectrum of immunopathogenic mechanisms underlying cow's milk allergy (CMA) is wide. Unprocessed, fresh cow's milk, like human breast milk, contains various tolerogenic factors that are impaired by industrial processing. Further studies focusing on the immunological consequences of milk processing are warranted to understand on a molecular basis to what extent processing procedures make single milk compounds into allergens. Elsevier Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines update - III - Cow's milk allergens and mechanisms triggering immune activation CC BY 4.0 International http://creativecommons.org/licenses/by/4.0/ application/pdf doi:10.1016/j.waojou.2022.100668 https://phaidra.vetmeduni.ac.at/o:2094 eng 2022 Jensen, Sebastian A. (Medical University of Vienna / University of Veterinary Medicine Vienna) WAO DRACMA guideline group, Nowak-Wegrzyn, Anna (Hassenfeld Childrens' Hospital New York) Jordakieva, Galateja (Medical University of Vienna) Baars, Ton (Utrecht University) Fiocchi, Alessandro (Bambino Gesù Children's Hospital Rome) Jensen-Jarolim, Erika (Medical University of Vienna / University of Veterinary Medicine Vienna) Venter, Carina (University of Colorado) Assa'ad, Amal H. (Cincinnati Children's Hospital Medical Center) Takkinen, Kristiina (VTT Technical Research Centre of Finland Ltd.) Roth-Walter, Franziska (Medical University of Vienna / University of Veterinary Medicine Vienna) Pranger, Christina L. (Medical University of Vienna / University of Veterinary Medicine Vienna) Passanisi, Stefano (University of Messina) Pali-Schöll, Isabella (Cincinnati Children's Hospital Medical Center / Private Clinics Döbling) Bovine Beta-Lactoglobulin; Alpha-Lactalbumin; Food Allergy; Protein; Anaphylaxis; Casein; Children; Receptor; Infants; Dermatitis article