Role of Human Leucocyte Antigen DQ in the Presentation of T Cell Epitopes in the Major Cow’s Milk Allergen αs1-Casein

Abstract

Background: Little is known about the association between human leucocyte antigen (HLA) and cow’s milk allergy (CMA). The aim of the present study was to determine the HLA restriction of T cell clones (TCCs) specific to αs1-casein, the most abundant milk protein, and to study possible HLA class II allele associations with CMA. Methods: αs1-Casein-specific TCCs were derived from 6 children with CMA, 9 atopic children without CMA and 5 non-atopic children. T cell epitope specificity was defined by stimulation with overlapping peptides, spanning the αs1-casein molecule. HLA restriction was determined in proliferation assays using antibodies blocking either HLA-DP, HLA-DQ or HLA-DR. HLA genotyping was performed in 32 subjects with CMA, 23 atopic and 22 non-atopic individuals. Results: Ten TCCs were restricted to HLA-DQ, 6 TCCs to HLA-DR and 4 TCCs to HLA-DP. The sequence in αs1-casein that was most immunogenic to T cells from children with CMA contained T cell epitopes restricted to DQB1*0201, DPB1*0401 and DRB1*1501. The DQB1*0501 allele frequency was lower in children with CMA than in non-atopic children, but this difference could not be confirmed in an additional group of subjects with and without CMA. Conclusions: HLA-DQ plays a substantial role in the presentation of T cell epitopes in αs1-casein. However, HLA class II allele frequencies do not show major differences between cow’s milk allergic, atopic and non-atopic subjects. T cell epitopes in the most immunogenic region are presented by various abundantly present HLA genotypes. Therefore, this sequence may be a suitable target for peptide immunotherapy.

Human Leukocyte Antigen (DR1)-DQB1*0501 and (DR15)-DQB1*0602 Haplotypes Are Associated with Humoral Responses to Early Food Allergens in Children

“…A variety of antigen-presenting HLA molecules could thus be expected to be involved in CMA. Studies on CM-specific T-cell clones from CMA patients indicated that antibodies to HLA-DR, HLA-DQ and HLA-DP could all restrict the proliferation of T-cell clones [37,38]. Therefore, it is apprehensible that an earlier study [8] as well as the present study detected no association between CMA and HLA haplotypes.…”

Peripheral Blood Immune Response Elicited by Beta-Lactoglobulin in Childhood Cow's Milk Allergy

“…Furthermore, a consistent number of the studies investigating the immune responses to CMP, and to food allergens in general, have used T-cell lines or T-cell clones, mostly derived from peripheral blood mononuclear cells (PBMCs) (5)(6)(7)(8)(9)(10)(11)(12). Albeit these are powerful techniques to investigate immune response to several antigens, and to define the stimulatory sequences in complex antigenic proteins, manipulation can occur in long-term cell cultures that could result in alteration of cell phenotypes and functions.…”

Twelve Myths About Food Allergies in Children

“…Во-первых, ␣S1 фракция казеина присутствует как в коровьем, так и в козьем молоке [4,15], при этом соотношение ␣S1 и ␣S2 фракции казеина генетиче-ски детерминировано и колеблется в довольно широких пределах [16,17]. Во-вторых, ␣S1-и ␣S2-казеин (как козьего, так и коровьего молока) относятся к мажорным аллергенам [18,19] и не отличаются по своей аллерген-ности [4]. Кроме того, у пациентов с персистирующей аллергией выявляются IgE-антитела к эпитопам как ␣S1-, так и ␣S2-казеина [20,21].…”