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在白细胞黏附抑制试验中,通过针对I类主要组织相容性复合体基因产物的单克隆抗体阻断人T淋巴细胞对自体癌提取物的反应。

Blocking of the response by human T-lymphocytes to extracts of autologous cancer by monoclonal antibody to Class-I major histocompatibility complex gene products in the leukocyte adherence inhibition assay.

作者信息

Shenouda G, Thomson D M

出版信息

Cancer Res. 1984 Jul;44(7):2762-8.

PMID:6609766
Abstract

In the leukocyte adherence inhibition (LAI) assay, about 34% of adherent T-cells from patients with breast cancer exhibit nonadherence to glass when incubated with extracts of autologous cancer but not with HLA-A, -B, and -C mismatched extracts of breast cancer. To determine whether the recognition by T-cells of tumor antigen was major histocompatibility complex restricted, major histocompatibility complex antigens in the cancer extracts or on the T-cells were coated with monoclonal antibody (MAb) to nonpolymorphic determinants. Nonadherence of T-cells was antagonized by coating the target cancer extracts with MAb to a common framework determinant of Class I HLA-A, -B, and -C antigens or to the nonpolymorphic beta 2-microglobulin, which is noncovalently associated with Class I antigens. By contrast, a MAb to a monomorphic determinant on HLA-DR antigens did not change the positive T-cell response. Moreover, coating the T-cells with MAb to HLA-A, -B, and -C did not inhibit the positive T-cell response. The positive LAI response of buffy coat peripheral blood leukocytes from patients with breast cancer to extracts of allogeneic breast cancer was not affected by coating the cancer extracts with the same MAb, indicating that MAb inhibited T-cell LAI specifically and that the antibody-dependent LAI response of buffy coat peripheral blood leukocytes was not major histocompatibility complex restricted. The results indicate that HLA-A, -B, and -C antigens in extracts of autologous breast cancer restrict the LAI response to tumor antigens of T-cells from patients with breast cancer.

摘要

在白细胞黏附抑制(LAI)试验中,与自体癌提取物一起孵育时,约34%的乳腺癌患者的贴壁T细胞不黏附于玻璃,而与HLA - A、- B和- C错配的乳腺癌提取物一起孵育时则不然。为了确定T细胞对肿瘤抗原的识别是否受主要组织相容性复合体限制,用针对非多态性决定簇的单克隆抗体(MAb)包被癌提取物或T细胞上的主要组织相容性复合体抗原。用针对I类HLA - A、- B和- C抗原共同构架决定簇或针对与I类抗原非共价结合的非多态性β2 -微球蛋白的MAb包被靶癌提取物,可拮抗T细胞的不黏附。相比之下,针对HLA - DR抗原单态性决定簇的MAb不会改变T细胞的阳性反应。此外,用针对HLA - A、- B和- C的MAb包被T细胞不会抑制T细胞的阳性反应。用相同的MAb包被癌提取物,乳腺癌患者血沉棕黄层外周血白细胞对同种异体乳腺癌提取物的阳性LAI反应不受影响,这表明MAb特异性抑制T细胞LAI,且血沉棕黄层外周血白细胞的抗体依赖性LAI反应不受主要组织相容性复合体限制。结果表明,自体乳腺癌提取物中的HLA - A、- B和- C抗原限制了乳腺癌患者T细胞对肿瘤抗原的LAI反应。

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