Daniel C, Grakoui A, Allen P M
Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Immunol. 1998 Apr 1;160(7):3244-50.
In this study, we explore the potential of altered peptide ligands (APLs) to modulate the alloresponse of CD4+ T cells using elements of the murine hemoglobin (Hb) Ag model. We first demonstrated that the T cell 2.102, specific for the Hb(64-76)/I-Ek complex, was alloreactive against splenocytes of the H-2p haplotype. Using Ab-blocking and transfection experiments, we further showed that this alloreactivity was restricted to the class II molecule I-Ep. We tested a panel of APLs previously shown to antagonize the Hb response of 2.102 and found that these peptides could also effectively inhibit the alloresponse to I-Ep. Importantly, these peptides were able to antagonize the alloresponse of naive T cells derived from mice transgenic for the 2.102 TCR, as well as Th1 and Th2 cell lines. The antagonism required the presence of both I-Ep and I-Ek on the same APC. Our study demonstrates the effectiveness of APLs to antagonize the primary alloresponse of specific T cells and provides a basis for the development of immunotherapeutics for use in transplantation and immune-mediated diseases.
在本研究中，我们利用小鼠血红蛋白（Hb）抗原模型的元件，探索改变肽配体（APL）调节CD4 + T细胞同种异体反应的潜力。我们首先证明，对Hb(64 - 76)/I-Ek复合物具有特异性的T细胞2.102，对H-2p单倍型的脾细胞具有同种异体反应性。通过抗体阻断和转染实验，我们进一步表明这种同种异体反应性仅限于II类分子I-Ep。我们测试了一组先前已证明可拮抗2.102的Hb反应的APL，发现这些肽也能有效抑制对I-Ep的同种异体反应。重要的是，这些肽能够拮抗源自2.102 TCR转基因小鼠的幼稚T细胞以及Th1和Th2细胞系的同种异体反应。这种拮抗作用需要同一抗原呈递细胞（APC）上同时存在I-Ep和I-Ek。我们的研究证明了APL拮抗特定T细胞原发性同种异体反应的有效性，并为开发用于移植和免疫介导疾病的免疫疗法提供了基础。
