Koyasu S, Lawton T, Novick D, Recny M A, Siliciano R F, Wallner B P, Reinherz E L
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA.
Proc Natl Acad Sci U S A. 1990 Apr;87(7):2603-7. doi: 10.1073/pnas.87.7.2603.
The role of the interaction of CD2 molecules with lymphocyte function-associated antigen 3 (LFA-3) in facilitating nominal antigen recognition by T lymphocytes was studied by utilizing an HLA-DR4-restricted CD4+ cytotoxic human T-cell clone specific for human immunodeficiency virus envelope glycoprotein gp120 as a responder and murine fibroblasts transfected with human class II major histocompatibility complex (MHC) and/or human LFA-3 molecules as antigen-presenting cells (APC). Although expression of the DR4 restriction element in fibroblasts is sufficient for T-cell recognition of a gp120 peptide as judged by induction of proliferation coexpression of human LFA-3 on DR4+ APC decreases the molar requirement of nominal antigen by greater than one order of magnitude. Both LFA-3 and the relevant class II MHC molecules are necessary for antigen-independent conjugate formation, but the binding is further enhanced by specific nominal antigen. CD2-LFA-3 interaction is independent of T-cell receptor-MHC interaction and contributes directly to the stabilized conjugate between the T cell and LFA-3-bearing APC; soluble CD2 and monoclonal antibodies to LFA-3 and CD2 reduce T-cell-APC binding to the level mediated by nominal antigen and MHC. During conjugate formation, CD2 but not CD3 molecules are reorganized into the cell-cell interaction site in an antigen-independent manner. Thus, reorganization and/or coassociation of CD2 with CD3 molecules is not essential for T-cell activation.
利用一株对人类免疫缺陷病毒包膜糖蛋白gp120特异的、受HLA - DR4限制的CD4 + 细胞毒性人T细胞克隆作为反应细胞，并以转染了人类II类主要组织相容性复合体（MHC）和/或人类淋巴细胞功能相关抗原3（LFA - 3）分子的鼠成纤维细胞作为抗原呈递细胞（APC），研究了CD2分子与LFA - 3相互作用在促进T淋巴细胞识别名义抗原中的作用。尽管通过增殖诱导判断，成纤维细胞中DR4限制元件的表达足以使T细胞识别gp120肽，但在DR4 + APC上共表达人类LFA - 3可使名义抗原的摩尔需求量降低一个以上数量级。LFA - 3和相关的II类MHC分子对于不依赖抗原的共轭体形成都是必需的，但特异性名义抗原可进一步增强这种结合。CD2 - LFA - 3相互作用独立于T细胞受体 - MHC相互作用，并直接有助于T细胞与携带LFA - 3的APC之间稳定的共轭体形成；可溶性CD2以及针对LFA - 3和CD2的单克隆抗体可将T细胞 - APC结合降低至由名义抗原和MHC介导的水平。在共轭体形成过程中，CD2而非CD3分子以不依赖抗原的方式重新组织到细胞 - 细胞相互作用位点。因此，CD2与CD3分子的重新组织和/或共缔合对于T细胞活化并非必不可少。
