The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing.
The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing.
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新的人类小型组织相容性抗原的免疫原性是由差异抗原加工引起的。
DOI：
10.1084/jem.193.2.195
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发表时间：
2001-01-15
影响因子：
15.3
通讯作者：
Riddell, S R
中科院分区：
文献类型：
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作者：
Brickner, A G;Warren, E H;Caldwell, J A;Akatsuka, Y;Golovina, T N;Zarling, A L;Shabanowitz, J;Eisenlohr, L C;Hunt, D F;Engelhard, V H;Riddell, S R
次要组织相容性抗原（Minor histocompatibility antigens，mHAgs）是HLA相合供、受者间器官和骨髓移植的重要障碍。在这里，我们报告了一个新的HLA-A*0201限制性的mHAg，HA-8的鉴定。将该mHAg命名为HA-8是基于Goulmy的命名法（Goulmy，E. 1996. Curr. Opin. Immunol.8：75-81）。该肽RTLDKVLEV来源于KIAA 0020，KIAA 0020是位于9号染色体上的功能未知的基因。KIAA 0020的多态性等位基因编码交替序列PTLDKVLEV和PTLDKVLEL。基因型分析表明，HA-8特异性细胞毒性T淋巴细胞（CTL）克隆SKH-13只承认的细胞表达的等位基因编码R在P1。然而，当PTLDKVLEV被脉冲到细胞上，或当编码该序列的小基因被用于人工将该肽转运到内质网中时，它被CTL几乎与RTLDKVLEV一样识别。这表明CTL不能识别表达KIAA 0020的PTLDKVLEV-coding等位基因的细胞是由于该肽不能被适当地蛋白水解或转运。与后一种可能性相一致，PTLDKVLEV及其较长的前体与RTLDKVLEV相比，通过与抗原加工相关的转运蛋白（TAP）转运较差。这些研究确定了一种新的人mHAg，并首次证明了微小的组织相容性差异可能是由于潜在抗原的加工改变而不是与相关主要组织相容性复合体分子或T细胞受体相互作用的差异。
Minor histocompatibility antigens (mHAgs) present a significant impediment to organ and bone marrow transplantation between HLA-identical donor and recipient pairs. Here we report the identification of a new HLA-A*0201–restricted mHAg, HA-8. Designation of this mHAg as HA-8 is based on the nomenclature of Goulmy (Goulmy, E. 1996. Curr. Opin. Immunol. 8:75–81). This peptide, RTLDKVLEV, is derived from KIAA0020, a gene of unknown function located on chromosome 9. Polymorphic alleles of KIAA0020 encode the alternative sequences PTLDKVLEV and PTLDKVLEL. Genotypic analysis demonstrated that the HA-8–specific cytotoxic T lymphocyte (CTL) clone SKH-13 recognized only cells that expressed the allele encoding R at P1. However, when PTLDKVLEV was pulsed onto cells, or when a minigene encoding this sequence was used to artificially translocate this peptide into the endoplasmic reticulum, it was recognized by CTLs nearly as well as RTLDKVLEV. This indicates that the failure of CTLs to recognize cells expressing the PTLDKVLEV-encoding allele of KIAA0020 is due to a failure of this peptide to be appropriately proteolyzed or transported. Consistent with the latter possibility, PTLDKVLEV and its longer precursors were transported poorly compared with RTLDKVLEV by transporter associated with antigen processing (TAP). These studies identify a new human mHAg and provide the first evidence that minor histocompatibility differences can result from the altered processing of potential antigens rather than differences in interaction with the relevant major histocompatibility complex molecule or T cell receptor.