Zlotnik A, Shimonkevitz R P, Gefter M L, Kappler J, Marrack P
J Immunol. 1983 Dec;131(6):2814-20.
We characterized an assay system to study the lymphokine-mediated induction of antigen-presenting ability in P388D1 cells. The ability of lymphokine-induced P388D1 macrophages to present antigen plus Id was measured by their ability to induce interleukin 2 production by antigen-specific, Id-restricted T cell hybridomas in the presence of the appropriate antigen. The production of IL 2 by the T cell hybridomas is known to be dependent on the expression of Ia antigens by the antigen-presenting cells. The results obtained suggest that a factor present in the supernatant of the T cell hybridoma FS7-20.6.18 is responsible for inducing the appearance of I-Ad and I-Ed on P388D1, measured by immunofluorescence, and the ability of the cell to present antigen in association with I-Ad or I-Ed. The factor mediating the induction of antigen-presenting ability is thought to be gamma-interferon, because the hybridoma FS7-20.6.18 is known to produce this lymphokine and the factor is sensitive to pH 2 incubation. gamma-Interferon produced by recombinant DNA technology was found to induce antigen-presenting ability in this assay; however, alpha- and beta-interferon were inactive. This observation suggests a unique immunoregulatory role for gamma-interferon. Using many T cell hybridomas in the assay, we were able to distinguish three groups: a) high avidity hybridomas that respond to antigen presented by uninduced P388D1 but show an enhanced response to antigen plus induced P388D1; b) medium avidity hybridomas that do not respond to antigen presented by uninduced P388D1; and c) low avidity hybridomas that show a limited response to antigen presented by induced P388D1, but the response of which increases if the P388D1 cells are induced for longer periods of time. These different patterns of response are believed to be dependent on the Ia antigen density expressed by the gamma-interferon-induced presenting cells, and suggest that the T cell receptors for Ag/Id display marked heterogeneity in their avidities for Ag/Id.
我们构建了一种检测系统，用于研究细胞因子介导的P388D1细胞抗原呈递能力的诱导过程。通过在合适的抗原存在下，细胞因子诱导后的P388D1巨噬细胞呈递抗原加Id的能力，来衡量其诱导抗原特异性、Id限制的T细胞杂交瘤产生白细胞介素2的能力。已知T细胞杂交瘤产生白细胞介素2依赖于抗原呈递细胞Ia抗原的表达。所得结果表明，T细胞杂交瘤FS7-20.6.18培养上清液中的一种因子，负责诱导P388D1细胞上I-Ad和I-Ed的出现（通过免疫荧光测定），以及细胞与I-Ad或I-Ed结合呈递抗原的能力。介导抗原呈递能力诱导的因子被认为是γ干扰素，因为已知杂交瘤FS7-20.6.18会产生这种细胞因子，且该因子对pH 2孵育敏感。在该检测中发现，通过重组DNA技术产生的γ干扰素可诱导抗原呈递能力；然而，α干扰素和β干扰素无活性。这一观察结果表明γ干扰素具有独特的免疫调节作用。在该检测中使用多种T细胞杂交瘤，我们能够区分出三组：a）高亲和力杂交瘤，对未诱导的P388D1呈递的抗原作出反应，但对抗原加诱导后的P388D1的反应增强；b）中等亲和力杂交瘤，对未诱导的P388D1呈递的抗原无反应；c）低亲和力杂交瘤，对诱导后的P388D1呈递的抗原反应有限，但如果P388D1细胞诱导时间更长，其反应会增强。这些不同的反应模式被认为取决于γ干扰素诱导的呈递细胞表达的Ia抗原密度，并表明Ag/Id的T细胞受体对Ag/Id的亲和力存在明显异质性。
