Amino acid substitutions can influence the natural killer (NK)-mediated recognition of HLA-C molecules. Role of serine-77 and lysine-80 in the target cell protection from lysis mediated by "group 2" or "group 1" NK clones.
Amino acid substitutions can influence the natural killer (NK)-mediated recognition of HLA-C molecules. Role of serine-77 and lysine-80 in the target cell protection from lysis mediated by "group 2" or "group 1" NK clones.
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DOI：
10.1084/jem.182.2.605
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发表时间：
1995-08-01
影响因子：
15.3
通讯作者：
Moretta, Lorenzo
中科院分区：
文献类型：
--
作者：
Biassoni, Roberto;Falco, Michela;Cambiaggi, Anna;Costa, Paola;Verdiani, Simonetta;Pende, Daniela;Conte, Romana;Di Donato, Carolina;Parham, Peter;Moretta, Lorenzo
自然杀伤（NK）细胞已显示出表达克隆分布的识别HLA I类等位基因的能力。先前定义的属于“组1”的NK克隆识别HLA-C*0401（Cw 4）和共享位置77处的Asn和位置80处的Lys的其它HLA-C等位基因。相反，“组2”NK克隆识别HLA-Cw*0302（Cw 3）和特征在于位置77处的Ser和位置80处的Asn的其它HLA-C等位基因。我们直接评估了这两个残基参与NK细胞克隆区分两组HLA-C等位基因的能力。为此，对Cw 3和Cw 4等位基因进行定点诱变。将Cw 3等位基因的典型氨基酸（Ser-77和Asn-80）替换为Cw 4中存在的氨基酸（Asn-77和Lys-80），产生了Cw 3突变体，该突变体不再被第2组NK细胞克隆识别，但被第1组识别克隆。分析含有单个氨基酸取代的Cw 3或Cw 4分子，表明Lys-80在由第1组克隆介导的识别中的作用和Ser-77在由第2组克隆介导的识别中的作用。这些结果表明，NK介导的HLA-C同种异型的特异性识别受到重链位置77和80处的单个天然氨基酸取代的影响。
Natural killer (NK) cells have been shown to express a clonally distributed ability to recognize HLA class I alleles. The previously defined NK clones belonging to "group 1" recognize HLA-C*0401 (Cw4) and other HLA-C alleles sharing Asn at position 77 and Lys at position 80. Conversely, the "group 2" NK clones recognize HLA-Cw*0302 (Cw3) and other HLA-C alleles characterized by Ser at position 77 and Asn at position 80. We assessed directly the involvement of these two residues in the capacity of NK cell clones to discriminate between the two groups of HLA-C alleles. To this end, Cw3 and Cw4 alleles were subjected to site-directed mutagenesis. Substitution of the amino acids typical of the Cw3 allele (Ser-77 and Asn-80) with those present in Cw4 (Asn-77 and Lys-80) resulted in a Cw3 mutant that was no longer recognized by group 2 NK cell clones, but that was recognized by group 1 clones. Analysis of Cw3 or Cw4 molecules containing single amino acid substitutions indicates roles for Lys-80 in recognition mediated by group 1 clones and for Ser-77 in recognition mediated by group 2 clones. These results demonstrate that NK-mediated specific recognition of HLA-C allotypes is affected by single natural amino acid substitutions at positions 77 and 80 of the heavy chain.
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影响因子：
15.3
作者：
ZEMMOUR, J;PARHAM, P
通讯作者：
PARHAM, P
DOI：
10.1084/jem.168.2.491
发表时间：
1988-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bottino C;Tambussi G;Ferrini S;Ciccone E;Varese P;Mingari MC;Moretta L;Moretta A
通讯作者：
Moretta A
影响因子：
2.7
作者：
LONG, EO;ROSENBRONSON, S;JARAQUEMADA, D
通讯作者：
JARAQUEMADA, D
影响因子：
15.3
作者：
MORETTA, A;PANTALEO, G;MINGARI, MC
通讯作者：
MINGARI, MC
影响因子：
--
作者：
Trinchieri G
通讯作者：
Trinchieri G