The underlying mechanism of milk allergies

When it comes to the ability to drink milk we have at least three types of individuals. People who can tolerate it and consume it without reaction; those who cannot consume milk because they lack enzymes for digestion of dairy products; and finally, people whose white blood cells develop an immune response to milk. Many scientists are intrigued by the molecular causes of reactions to milk. Among the proteins found in milk, the beta-lactoglobulin protein (Bos d 5) is known to help activate T-lymphocytes. Bos d 5 belongs to the lipocalin-family, a group of proteins with molecular pockets called siderophores. The siderophores of Bos d 5, specifically, are able to bind with iron complexes. Thus, Bos d 5 can be found in two forms: an “apo” state (without an iron-siderophore) and the “holo” state (with an iron-siderophore). Scientists wanted to test the immune-modulatory properties of Bos d 5 in either form to see if that was linked with milk allergies. Under controlled lab conditions, scientists were able to isolate the apo and holo forms of Bos d 5. Scientists proceeded to perform an experiment in which the white blood cells of 25 patients were exposed to 3 treatments: 1) exposure to phorbol12-myristate13-acetate (PMA), a compound that assists in T-cell activation; 2) exposure to PMA and apo-Bos d 5; 3) exposure to PMA and holo-Bos d 5. To guarantee that only T-lymphocytes were sampled, scientists searched for cells that contained the cell differentiation factor 3 (CD3) typical of T-cells, and then examined the activation of the two major subpopulations of T-cells, CD4 and CD8 (Figure 1).

Figure 1. Percentage of activated CD3+CD4+ cells and CD3+CD8+ cells after exposure to PMA, PMA plus apo-Bos d 5, and holo-Bos d 5. Bars indicate statistical comparison, ends of each bar are place over groups being compared. Statistical significance is indicate as follows: P<0.01, **P<0.0001, NS = not significant.