Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules.
Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules.
复制标题
HLA-B35 和 HLA-B38 分子呈递人类次要组织相容性抗原。
DOI：
10.1073/pnas.87.7.2583
复制
发表时间：
1990
影响因子：
11.1
通讯作者：
Masafumi Takiguchi
中科院分区：
文献类型：
--
作者：
J. Yamamoto;A. Kariyone;Nobuo Akiyama;Kyoichi Kano;Masafumi Takiguchi
人类次要组织相容性抗原（hmHAs）特异性的细胞毒性T淋巴细胞（CTL）克隆产生于一名患者，该患者移植了来自其母亲和两个hla相同的姐妹的肾脏。在产生的8个CTL克隆中，4个识别了在母亲和姐姐3（第二个供体）细胞上表达的hmHA (hmHA-1)；2例在父亲、妹妹2（第三个供体）和妹妹3的细胞上识别另一种抗原（hmHA-2）；剩下的两个克隆在父亲和妹妹的细胞上还识别出另一种抗原（hmHA-3）。小组研究显示，hmHA-1的CTL识别受HLA-B35的限制，hmHA-2和hmHA-3的识别受HLA-B38的限制。hmha -1特异性CTL克隆的HLA-B35限制性被证实，它们可以杀死转染HLA-B35的HLA-A空/HLA-B空Hmy2CIR靶标，但不能杀死转染Hmy2CIR靶标的HLA-B51、-Bw52或-Bw53。这些数据表明，HLA-B35和-Bw53之间α -1结构域上与Bw4/Bw6表位相关的5个氨基酸取代在hmHA-1与HLA-B35分子的关系中起关键作用。hmHA-1特异性ctl未能杀死表达HLA-B35/51嵌合分子的Hmy2CIR细胞，这些嵌合分子由HLA-B35的α 1结构域和其他HLA-B51结构域组成，这表明α 2结构域上的8个残基也影响了hmHA-1与HLA-B35分子的相互作用。
Cytotoxic T lymphocyte (CTL) clones specific for human minor histocompatibility antigens (hmHAs) were produced from a patient who had been grafted with the kidneys from his mother and two HLA-identical sisters. Of eight CTL clones generated, four recognized an hmHA (hmHA-1) expressed on cells from the mother and sister 3 (second donor); two recognized another antigen (hmHA-2) on cells from the father, sister 2 (third donor), and sister 3; and the remaining two clones recognized still another antigen (hmHA-3) on cells from the father and sister 3. Panel studies revealed that CTL recognition of hmHA-1 was restricted by HLA-B35 and that of hmHA-2 and hmHA-3 was restricted by HLA-B38. The HLA-B35 restriction of the hmHA-1-specific CTL clones was substantiated by the fact that they killed HLA-A null/HLA-B null Hmy2CIR targets transfected with HLA-B35 but not HLA-B51, -Bw52, or -Bw53 transfected Hmy2CIR targets. These data demonstrated that the five amino acids substitutions on the alpha 1 domain between HLA-B35 and -Bw53, which are associated with Bw4/Bw6 epitopes, play a critical role in the relationship of hmHA-1 to HLA-B35 molecules. The fact that the hmHA-1-specific CTLs failed to kill Hmy2CIR cells expressing HLA-B35/51 chimeric molecules composed of the alpha 1 domain of HLA-B35 and other domains of HLA-B51 indicated that eight residues on the alpha 2 domain also affect the interaction of hmHA-1 and the HLA-B35 molecules.