Recognition of class I major histocompatibility complex molecules by Ly-49: Specificities and domain interactions
Recognition of class I major histocompatibility complex molecules by Ly-49: Specificities and domain interactions
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DOI：
10.1084/jem.183.4.1553
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发表时间：
1996-04-01
影响因子：
15.3
通讯作者：
Takei, F
中科院分区：
文献类型：
--
作者：
Brennan, J;Mahon, G;Takei, F
Ly-49是由小鼠6号染色体上的一个基因簇编码的II型跨膜蛋白家族。该家族的一个成员，Ly-49A，由自然杀伤（NK）细胞亚群表达，与I类主要组织相容性复合体（MHC）分子结合，阻断携带适当H-2抗原的靶细胞的杀伤。在这里，我们展示了这个家族的另一个成员，由NK细胞亚群Ly-49C表达，识别H-2(b)和H-2(d)结构，这些结构与Ly-49A识别的结构不同，并与之重叠。Ly-49A和C及其I类配体之间的相互作用被抗体5E6， YE1/48， YE1/32和A1完全阻断，这些抗体都被发现识别含有碳水化合物识别域（CRD）的表位。然而，细胞-细胞结合试验显示，一类结合特异性是由CRD和19个氨基酸邻近区域的序列组合赋予的。我们还研究了Ly-49A和C是否在表达这两种受体的细胞上形成二聚体的问题。当在COS细胞上共表达时，序贯免疫沉淀表明这些受体完全作为同二聚体配对，没有证据表明存在异二聚体结构。这些观察结果为Ly-49家族的生化性质以及Ly-49C对NK细胞的受体功能提供了深入的了解。
Ly-49 is a family of type II transmembrane proteins encoded by a gene cluster on murine chromosome 6. One member of this family, Ly-49A, is expressed by a natural killer (NK) cell subset, binds to class I major histocompatibility complex (MHC) molecules, and blocks the killing of target cells bearing the appropriate H-2 antigens. Here we show that another member of this family which is expressed by an NK cell subset, Ly-49C, recognizes H-2(b) and H-2(d) structures which are distinct from and overlapping with those recognized by Ly-49A. Interactions between Ly-49A and C and their class I ligands are entirely blocked by the antibodies 5E6, YE1/48, YE1/32, and A1, all of which were found to recognize epitopes contained within the carbohydrate recognition domain (CRD). However, cell-cell binding assays revealed that class I binding specificity is conferred by a combination of sequences within both the CRD and a 19-amino acid adjacent region. We also investigated the question of whether Ly-49A and C form dimers on cells which express both receptors. When coexpressed on COS cells, sequential immunoprecipitation demonstrated that these receptors pair exclusively as homodimers, with no evidence for heterodimeric structures. These observations provide insight into both the biochemical nature of the Ly-49 family as well as the receptor functions of Ly-49C on NK cells.