Melanocyte-associated T cell epitopes can function as autoantigens for transfer of alopecia areata to human scalp explants on Prkdcscid mice
Melanocyte-associated T cell epitopes can function as autoantigens for transfer of alopecia areata to human scalp explants on Prkdcscid mice
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DOI：
10.1046/j.0022-202x.2001.01583.x
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发表时间：
2001-12-01
影响因子：
6.5
通讯作者：
Kalish, RS
中科院分区：
文献类型：
--
作者：
Gilhar, A;Landau, M;Kalish, RS
斑秃是一种组织受限的自身免疫性疾病，影响毛囊，导致脱发。这项研究的目的是验证斑秃自身抗原与黑素细胞相关的假设。在人头皮外植体/Prkd(SCID)CB-17小鼠移植系统中测试了潜在的自身抗原。将斑秃患者头皮T细胞与抗原提呈细胞和白介素2共同培养。然后将T细胞注射到SCID小鼠的自体头皮移植中，并测量毛发的再生。以毛囊匀浆作为自身抗原对照。与黑色素瘤匀浆一起培养的T细胞导致头发生长显著减少(P<；0.01经方差分析)。然后用人类白细胞抗原A2阳性斑秃患者的皮损T细胞检测人类白细胞抗原A2限制性黑素细胞多肽表位。在对6名患者进行的两项实验中，黑素细胞肽激活的T细胞显著减少了毛发的再生数量(P<；0.001)。注射的头皮移植物显示斑秃的组织学和免疫化学改变。最一致的多肽自身抗原是gp100衍生的G9-209和G9-280多肽，以及MART-1(27-35)。黑素细胞多肽表位可以作为斑秃的自身抗原。识别出多个多肽，提示表位分布。
Alopecia areata is a tissue restricted autoimmune condition affecting the hair follicle, resulting in hair loss. The goal of this study was to test the hypothesis that the autoantigen of alopecia areata is melanocyte associated. Potential autoantigens were tested in the human scalp explant/Prkd(scid) CB-17 mouse transfer system. Scalp T cells froth lesional (bald) alopecia areata scalp were cultured with antigen-presenting cells, and antigen, along with interleukin-2. The T cells were then injected into autologous lesional scalp grafts on SCID mice, and hair regrowth was measured. Hair follicle homogenate was used as an autoantigen control. T cells cultured with melanoma homogenate induced statistically significant reduction in hair growth (p < 0.01 by ANOVA). HLA-A2-restricted melanocyte peptide epitopes were then tested with lesional scalp T cells from HLA-A2-positive alopecia areata patients. Melanocyte-peptide-activated T cells significantly reduced the number of hairs regrowing in two experiments with six patients (p < 0.001 by ANOVA). Injected scalp grafts showed histologic and immunochemical changes of alopecia areata. The most consistent peptide autoantigens were the Gp100-derived G9-209 and G9-280 peptides, as well as MART-1 (27-35). Melanocyte peptide epitopes can function as autoantigens for alopecia areata. Multiple peptides were recognized, suggesting epitope spreading.