Harris P E, Liu Z, Colovai A I, Kinne J, Maffei A, Febles A, Suciu-Foca N
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10027, USA.
Int Immunol. 1996 Aug;8(8):1265-71. doi: 10.1093/intimm/8.8.1265.
CD45 is a transmembrane protein tyrosine phosphatase expressed by all lymphoid cells including T cells. Substantial experimental data has shown that CD45 maintains a permissive state for TCR signaling. The highly glycosylated extracellular domain of CD45 may be the site of interaction with regulatory lectin-like counter-receptors on antigen-presenting cells. The mAb NDA5, recognizing a unique but broadly distributed epitope of CD45, was used to study the possible immunoregulatory role of CD45 during anti-CD3 and antigen-specific CD4+ T cell activation. In vitro priming of peripheral blood mononuclear cells with peptide antigens in the presence of mAb NDA5 results in a higher frequency of antigen-specific T cells. The responses of both naive and memory T cells to peptide antigens were sensitive to mAb NDA5-enhanced priming. Anti-CD3 activation of normal resting T cells, in the presence of mAb NDA5, resulted in enhancement of tyrosine phosphorylation of specific intracellular proteins associated with TCR signal transduction. In cultures without antigen, mAb NDA5 down-regulated the cell surface expression of both CD3 and CD4, yet did not stimulate proliferation of resting T cells. Together these results suggest that engagement of CD45 during in vitro priming has a significant effect on the development of antigen-specific T cell populations.
CD45是一种跨膜蛋白酪氨酸磷酸酶，由包括T细胞在内的所有淋巴细胞表达。大量实验数据表明，CD45维持TCR信号传导的许可状态。CD45高度糖基化的细胞外结构域可能是与抗原呈递细胞上调节性凝集素样反受体相互作用的位点。单克隆抗体NDA5可识别CD45独特但广泛分布的表位，用于研究CD45在抗CD3和抗原特异性CD4+T细胞活化过程中可能的免疫调节作用。在单克隆抗体NDA5存在的情况下，用肽抗原对外周血单个核细胞进行体外致敏，可使抗原特异性T细胞的频率更高。幼稚T细胞和记忆T细胞对肽抗原的反应均对单克隆抗体NDA5增强的致敏敏感。在单克隆抗体NDA5存在的情况下，正常静息T细胞的抗CD3活化导致与TCR信号转导相关的特定细胞内蛋白酪氨酸磷酸化增强。在无抗原的培养物中，单克隆抗体NDA5下调CD3和CD4的细胞表面表达，但不刺激静息T细胞增殖。这些结果共同表明，体外致敏过程中CD45的结合对抗抗原特异性T细胞群体的发育有显著影响。
