Inoue R, Matsushita S, Kaneko H, Shinoda S, Sakaguchi H, Nishimura Y, Kondo N
Department of Paediatrics, Gifu University School of Medicine, Tsukasa-machi 40, Gifu 500, Japan.
Clin Exp Allergy. 2001 Jul;31(7):1126-34. doi: 10.1046/j.1365-2222.2001.01135.x.
Cow's milk allergy impairs the health and development of many infants since it deprives them of adequate nutrition. Cow's milk fractions contain many allergens, and beta-lactoglobulin (BLG) is one of the major allergens.
The purpose of this study was to determine T cell epitopes, antigen-presenting molecules and cytokine production by T cells in relation to BLG. The results can provide new therapeutic possibilities of using analogue peptides of BLG for infants with cow's milk allergy.
Using a mixture of a panel of overlapping synthetic peptides that cover the entire BLG molecule, we established polyclonal BLG-specific short-term T cell lines and clones from peripheral blood mononuclear cells of four patients with allergy to cow's milk carrying most of the common human leucocyte antigen (HLA) haplotypes seen in the Japanese population. We then identified the T cell epitopes and antigen-presenting molecules, and measured the production of cytokines interleukin (IL)-4, IL-5 and interferon-gamma in the culture supernatants.
The T cell lines established from the four patients responded to seven different peptides. Three of the peptides stimulated the T cells of two donors, regardless of the HLA types. The patterns of inhibition of the proliferative responses of the cell lines by anti-HLA class II antibodies were heterogeneous; three were mainly inhibited by anti-HLA-DR mAbs, and the other was inhibited by anti-HLA-DQ mAbs. High levels of IL-5 were produced by these T cell lines.
Patients' T cells recognized BLG in association with a variety of HLA-DR or -DQ as antigen-presenting molecules. Although some peptides did have a more potent T cell stimulatory activity than others, the T cell receptor ligands formed with the BLG molecule are heterogeneous. Peptides for the desensitization of T cells of the patients with cow's milk allergy need to be designed keeping in mind the different requirements in different ethnic groups.
牛奶过敏会损害许多婴儿的健康和发育，因为它使婴儿无法获得充足的营养。牛奶组分含有多种过敏原，β-乳球蛋白（BLG）是主要过敏原之一。
本研究旨在确定与BLG相关的T细胞表位、抗原呈递分子以及T细胞产生的细胞因子。研究结果可为牛奶过敏婴儿使用BLG类似肽提供新的治疗可能性。
我们使用一组覆盖整个BLG分子的重叠合成肽混合物，从四名对牛奶过敏且携带日本人群中常见的大多数人类白细胞抗原（HLA）单倍型的患者的外周血单个核细胞中建立了多克隆BLG特异性短期T细胞系和克隆。然后我们鉴定了T细胞表位和抗原呈递分子，并测量了培养上清液中白细胞介素（IL）-4、IL-5和干扰素-γ的产生情况。
从这四名患者建立的T细胞系对七种不同的肽有反应。其中三种肽刺激了两名供体的T细胞，与HLA类型无关。抗HLA II类抗体对细胞系增殖反应的抑制模式各不相同；三种主要被抗HLA-DR单克隆抗体抑制，另一种被抗HLA-DQ单克隆抗体抑制。这些T细胞系产生了高水平的IL-5。
患者的T细胞将与多种HLA-DR或-DQ结合的BLG识别为抗原呈递分子。虽然一些肽比其他肽具有更强的T细胞刺激活性，但与BLG分子形成的T细胞受体配体是异质性的。设计牛奶过敏患者T细胞脱敏肽时需要考虑不同种族的不同需求。
