In vivo dimeric association of class I MHC heavy chains. Possible relationship to class I MHC heavy chain-beta 2-microglobulin dissociation.
In vivo dimeric association of class I MHC heavy chains. Possible relationship to class I MHC heavy chain-beta 2-microglobulin dissociation.
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DOI：
10.4049/jimmunol.151.1.159
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发表时间：
1993-07
影响因子：
4.4
通讯作者：
G. G. Capps-G.;B. E. Robinson;K. Lewis;M. Zúñiga
中科院分区：
文献类型：
--
作者：
G. G. Capps-G.;B. E. Robinson;K. Lewis;M. Zúñiga
人们认为I类MHC分子在体内以与抗原肽相关或不相关的I类MHC重链-β2-m异二聚体和游离的I类MHC重链的形式存在。现在发现 I 类 MHC 分子也以另一种结构类型存在：重链-重链二聚体。生化研究表明，重链二聚体通过保守的细胞质结构域半胱氨酸进行二硫键连接。 H-2Ld、H-2Db 和 H-2Dd I 类二聚体无法与某些 α 1 和 α 2 结构域特异性抗体发生反应。此外，虽然β2-m特异性抗体共沉淀I类MHC重链，但它们不共沉淀I类MHC重链二聚体。脉冲追踪研究表明，重链二聚体的形成发生在 β 2-m+ 和 β 2-m- 细胞中 I 类 MHC 分子生物合成的不同点：在 β 2-m+ 细胞中，重链二聚体在 I 类分子穿过内侧高尔基体池后形成，而在 β 2-m- 细胞中，它们立即形成。用外源 β2-m 培养 β2-m+ 细胞可防止 H-2Ld/Db 重链二聚体的形成。我们得出结论，二聚体的形成是由于 β2-m 丢失或不可用而发生的。 I 类 MHC 重链二聚化可能提供一种去除免疫功能障碍分子的机制。
Class I MHC molecules have been thought to occur in vivo both as class I MHC heavy chain-beta 2-m heterodimers, which are or are not associated with antigenic peptide, and as free class I MHC heavy chains. Class I MHC molecules are now found also to occur in another type of structure: a heavy chain-heavy chain dimer. Biochemical studies show that heavy chain dimers are disulfide-linked via a conserved cytoplasmic domain cysteine. H-2Ld, H-2Db, and H-2Dd class I dimers fail to react with certain alpha 1 and alpha 2 domain-specific antibodies. Furthermore, although beta 2-m-specific antibodies coprecipitate class I MHC heavy chains, they do not coprecipitate class I MHC heavy chain dimers. Pulse-chase studies show that heavy chain dimer formation occurs at different points in the biosynthesis of class I MHC molecules in beta 2-m+ and beta 2-m- cells: in beta 2-m+ cells, heavy chain dimers form after the class I molecules have traversed the medial Golgi cisternae, whereas in beta 2-m- cells they form immediately. Culturing of beta 2-m+ cells with exogenous beta 2-m prevents the formation of H-2Ld/Db heavy chain dimers. We conclude that dimer formation occurs as a consequence of loss or unavailability of beta 2-m. Class I MHC heavy chain dimerization may provide a mechanism for removal of immunologically dysfunctional molecules.