Analysis of the requirement for beta 2-microglobulin for expression and formation of human CD1 antigens
Analysis of the requirement for beta 2-microglobulin for expression and formation of human CD1 antigens
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DOI：
10.1002/eji.1830270611
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发表时间：
1997-06-01
影响因子：
5.4
通讯作者：
Stockinger, H
中科院分区：
文献类型：
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作者：
Bauer, A;Huttinger, R;Stockinger, H
人CD 1形成一组与主要组织相容性复合体（MHC）蛋白具有同源性的非多态性白细胞表面分子。最近在人类和小鼠中的发现证明了CD 1分子呈递非肽组分如脂质或脂聚糖以及肽的能力。我们研究了β 2-微球蛋白（β 2 m）在经典的人CD 1蛋白CD 1a、CD 1b和CD 1c表达中的参与。使用腺病毒增强型受体介导的转移感染系统，用CD 1a、CD 1b或CD 1c DNA单独或与β 2 m组合瞬时转染β 2 m缺陷型人黑素瘤细胞系FO-1。只有FO-1细胞与CD 1 + β 2 m共转染才能通过单克隆抗体（mAb）检测到CD 1 Ag。这表明CD 1 mAb识别的决定簇依赖于β 2 m，并提出了是否可以表达无β 2 m形式的CD 1的问题。因此，为了使CD 1分子表达独立于β 2 m可视化，我们表达了标记的重组形式。只有当β 2 m共转染时，在C末端用小肽标记的全长CD 1b构建体才被转运到质膜。β 2 m参与CD 1的转运，通过在三种不同细胞类型中表达可溶形式的CD 1a、CD 1b和CD 1c得到证实。与标记的全长CD 1b类似，可溶性CD 1构建体的分泌严格依赖于β 2 m。可溶性CD 1嵌合体作为与内源性β 2 m的复合物分泌。因此，类似于其对MHC I类表达的作用，β 2 m对于经典的人CD 1分子CD 1a、CD 1b和CD 1c的加工和表面转运是必需的。
Human CD1 form a group of nonpolymorphic leukocyte surface molecules with homology to major histocompatibility complex (MHC) proteins. Recent findings in human and in mouse demonstrate the capacity of CD1 molecules to present nonpeptide components like lipids or lipoglycans as well as peptides. We studied the involvement of beta 2-microglobulin (beta 2m) in expression of the classic human CD1 proteins CD1a, CD1b, and CD1c. The beta 2m-deficient human melanoma cell line FO-1 was transiently transfected with either CD1a, CD1b, or CD1c DNA alone, or in combination with beta 2m using the adenovirus-enhanced receptor-mediated transfer infection system. Only co-transfection of FO-1 cells with CD1 + beta 2m resulted in the detection of CD1 Ag by monoclonal antibodies (mAb). This indicated that CD1 mAb recognized determinants are dependent on beta 2m and raised the question whether beta 2m-free forms of CD1 can be expressed. Therefore, to visualize CD1 molecule expression independently of beta 2m, we expressed tagged recombinant forms. A full-length CD1b construct tagged at the very C terminus with a small peptide was transported to the plasma membrane only when beta 2m was co-transfected. beta 2m involvement in the transport of CD1 was confirmed by expression of soluble forms of CD1a, CD1b, and CD1c in three different cell types. Analogous to tagged full-length CD1b, secretion of the soluble CD1 constructs was strictly dependent on beta 2m. The soluble CD1 chimeras were secreted as complexes with endogenous beta 2m. Thus, similar to its role for MHC class I expression, beta 2m is essential for processing and surface transport of the classic human CD1 molecules CD1a, CD1b, and CD1c.