Maio M, Gulwani B, Tombesi S, Langer J A, Duigou G J, Kerbel R S, Fisher P B, Ferrone S
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
J Immunol. 1988 Aug 1;141(3):913-20.
This study has shown for the first time an association between the metastatic properties of two autologous melanoma cell lines and their susceptibility to induction of HLA class II Ag by IFN-gamma. After in vitro incubation with IFN-gamma the melanoma cell line MeWo did not acquire reactivity with anti-HLA class II antibodies, whereas its metastatic variant MeM 50-10 did. The differential susceptibility to induction of HLA class II Ag on the two cell lines cannot be accounted for by either differences in the number and affinity of IFN-gamma receptors or in the sensitivity to IFN-gamma, but most likely reflects an intrinsic property of each cell line. Serologic and immunochemical investigations with anti HLA-DR, DQ, and DP mAb have indicated that only HLA-DR Ag are induced by IFN-gamma on MeM 50-10 cells. Northern blot analysis with HLA-DR beta, DQ beta, and DP beta probes suggest that different mechanisms underlie the differential susceptibility to induction by IFN-gamma of the gene products of the HLA-D region. The regulatory mechanism(s) that control the expression of HLA class II Ag appear to be different from those controlling the expression of the melanoma-associated Ag tested, inasmuch as the modulation of the latter by IFN-gamma did not differ on the two melanoma cell lines.
本研究首次揭示了两种自体黑色素瘤细胞系的转移特性与其对γ干扰素诱导HLA - II类抗原的易感性之间的关联。在与γ干扰素进行体外孵育后,黑色素瘤细胞系MeWo未获得与抗HLA - II类抗体的反应性,而其转移变体MeM 50 - 10则获得了这种反应性。两种细胞系对诱导HLA - II类抗原的不同易感性,既不能用γ干扰素受体数量和亲和力的差异,也不能用对γ干扰素的敏感性差异来解释,而很可能反映了每个细胞系的内在特性。用抗HLA - DR、DQ和DP单克隆抗体进行的血清学和免疫化学研究表明,在MeM 50 - 10细胞上,γ干扰素仅诱导HLA - DR抗原。用HLA - DRβ、DQβ和DPβ探针进行的Northern印迹分析表明,HLA - D区域基因产物对γ干扰素诱导的不同易感性存在不同的机制。控制HLA - II类抗原表达的调控机制似乎与控制所检测的黑色素瘤相关抗原表达的机制不同,因为γ干扰素对后一种抗原的调节在两种黑色素瘤细胞系上并无差异。