HLA-F complex without peptide binds to MHC class I protein in the open conformer form.
HLA-F complex without peptide binds to MHC class I protein in the open conformer form.
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DOI：
10.4049/jimmunol.1000078
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发表时间：
2010-06-01
期刊：
影响因子：
--
通讯作者：
Geraghty DE
中科院分区：
文献类型：
--
作者：
Goodridge JP;Burian A;Lee N;Geraghty DE
在人类中，HL A-F的多态水平很低，在灵长类动物中高度保守，这表明在免疫反应中具有保守的功能。在本研究中，我们通过直接测量天然的人类白细胞抗原-F的多肽结合量来探讨B-淋巴细胞和活化淋巴细胞表面的人类白细胞抗原-F的结构。我们的发现表明，人类白细胞抗原-F的表达不依赖于结合多肽，至少在与人类白细胞抗原-E或经典MHC-I相似的多肽复杂性方面是如此。作为对天然人类白细胞抗原F结构的进一步探索，我们使用了一些互补的方法来探索在细胞表面、细胞内以及在直接的物理生化测量中人类白细胞抗原F与其他分子的相互作用。这一分析表明，HLAF的表面表达与MHC-I重链(HC)的表达一致，并且受MHC-I重链结构的干扰而下调。进一步可以直接证明MHC-I只有在无肽的开放构象而不是三聚体复合体的形式下才与人类白细胞抗原F相互作用。通过免疫共沉淀和表面等离子体共振直接观察到这种相互作用，并通过符合的四聚体和MHC-IHC共定位间接观察到这种相互作用。综上所述，这些数据表明，HLAF的表达不依赖于多肽，并且MHC-IHC的特异性物理相互作用在激活的淋巴细胞中MHC-IHC的表达功能中发挥了作用。
HLA-F has very low levels of polymorphism in humans and is highly conserved among primates suggesting a conserved function in the immune response. In this study we probed the structure of HLA-F on the surface of B-LCLs and activated lymphocytes by direct measurement of peptide binding of native HLA-F. Our findings suggested that HLA-F is expressed independently of bound peptide, at least with respect to peptide complexity profiles similar to those of either HLA-E or classical MHC-I. As a further probe of native HLA-F structure, we used a number of complementary approaches to explore the interactions of HLA-F with other molecules, at the cell surface, intracellularly, and in direct physical biochemical measurements. This analysis demonstrated that HLA-F surface expression was coincident with MHC-I heavy chain (HC) expression and was down regulated upon perturbation of MHC-I HC structure. It was further possible to directly demonstrate that MHC-I would only interact with HLA-F when in the form of open conformer free of peptide and not as trimeric complex. This interaction was directly observed by co-immunoprecipitation and by surface plasmon resonance and indirectly on the surface of cells through coincident tetramer and MHC-I HC co-localization. Together these data suggest that HLA-F is expressed independent of peptide and that a physical interaction specific to MHC-I HC plays a role in the function of MHC-I HC expression in activated lymphocytes.
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影响因子：
4.4
作者：
CICCONE, E;PENDE, D;MORETTA, L
通讯作者：
MORETTA, L
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
DOI：
10.1073/pnas.89.9.3947
发表时间：
1992-05-01
影响因子：
11.1
作者：
ISHITANI, A;GERAGHTY, DE
通讯作者：
GERAGHTY, DE
DOI：
10.1016/0167-5699(95)80063-8
发表时间：
1995-01-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
ACCOLLA, RS;ADORINI, L;GUARDIOLA, J
通讯作者：
GUARDIOLA, J
影响因子：
4.3
作者：
DEMARIA, S;SCHWAB, R;BUSHKIN, Y
通讯作者：
BUSHKIN, Y