Bismuth G, Gouy H, Karr R W, Debré P
Laboratoire d'Immunologie Cellulaire et Tissulaire, CNRS UA 186, Hôpital de la Pitié-Salpêtrière, Paris, France.
Hum Immunol. 1990 Jul;28(3):271-83. doi: 10.1016/0198-8859(90)90057-v.
L cell fibroblasts transfected with HLA class II cDNA clones isolated from a cDNA library produced from a DR7 homozygous cell line were used as antigen-presenting cells (APC) for three HLA DR-restricted, diphtheria toxoid-specific T-cell clones in order to assess the antigen-presenting ability of the transfectants and to define the class II restriction of each clone. Class II-expressing transfectants are capable of presenting antigen to antigen-specific T-cell clones, although the transfectants are less efficient at antigen presentation than conventional APC. Paraformaldehyde fixation of transfectants prior to antigen pulsing abrogated antigen presentation, demonstrating that the transfectants require antigen processing. Antigen presentation by transfectants is completely inhibited by CD4-specific monoclonal antibodies (mAb) and one of four DR-specific mAb, whereas antigen presentation by conventional APC is only partially inhibited. Both the DR alpha:DR7 beta 1 and DR alpha:DR beta 4 (DR omega 53) molecules of the DR7 allotype serve as restriction elements for the diphtheria toxoid-specific T-cell clones. One clone is restricted by the DR7 beta 1 molecule, another clone by the DR beta 4(DR omega 53) molecule, and a third clone by a cross-reactive T cell epitope on DR7 beta 1 and DR beta 4(DR omega 53) molecules. The two DR beta 4(DR omega 53)-restricted clones react, however, differently with a panel of HLA-DR DR omega 53-positive human peripheral blood lymphocytes used as APC. Therefore the data presented here clearly document that the DR beta 4 (DR omega 53) chain may serve as restriction elements for DT-specific T-cell clones. They also provide the first evidence for functional cross-reactivity of the products of two different DR beta loci and in addition emphasize the high complexity of the supertypic HLA-DR omega 53 specificity.
从一个由DR7纯合细胞系构建的cDNA文库中分离出HLA II类cDNA克隆，并用其转染L细胞成纤维细胞，将这些转染细胞用作三种HLA DR限制的、白喉类毒素特异性T细胞克隆的抗原呈递细胞（APC），以评估转染细胞的抗原呈递能力，并确定每个克隆的II类限制。表达II类分子的转染细胞能够将抗原呈递给抗原特异性T细胞克隆，尽管转染细胞在抗原呈递方面比传统APC效率低。在抗原脉冲之前用多聚甲醛固定转染细胞可消除抗原呈递，表明转染细胞需要抗原加工。转染细胞的抗原呈递被CD4特异性单克隆抗体（mAb）和四种DR特异性mAb中的一种完全抑制，而传统APC的抗原呈递仅被部分抑制。DR7同种异型的DRα:DR7β1和DRα:DRβ4（DRω53）分子均作为白喉类毒素特异性T细胞克隆的限制元件。一个克隆受DR7β1分子限制，另一个克隆受DRβ4（DRω53）分子限制，第三个克隆受DR7β1和DRβ4（DRω53）分子上的交叉反应性T细胞表位限制。然而，两个受DRβ4（DRω53）限制的克隆与一组用作APC的HLA-DR DRω53阳性人外周血淋巴细胞反应不同。因此，此处呈现的数据清楚地证明DRβ4（DRω53）链可能作为DT特异性T细胞克隆的限制元件。它们还首次提供了两种不同DRβ基因座产物功能交叉反应性的证据，此外还强调了超型HLA-DRω53特异性的高度复杂性。
