HUMAN T-CELL LYMPHOTROPIC VIRUS (HTLV)-RELATED ENDOGENOUS SEQUENCE, HRES-1, ENCODES A 28-KDA PROTEIN - A POSSIBLE AUTOANTIGEN FOR HTLV-I GAG-REACTIVE AUTOANTIBODIES
HUMAN T-CELL LYMPHOTROPIC VIRUS (HTLV)-RELATED ENDOGENOUS SEQUENCE, HRES-1, ENCODES A 28-KDA PROTEIN - A POSSIBLE AUTOANTIGEN FOR HTLV-I GAG-REACTIVE AUTOANTIBODIES
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DOI：
10.1073/pnas.89.5.1939
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发表时间：
1992-03-01
影响因子：
11.1
通讯作者：
PERL, A
中科院分区：
文献类型：
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作者：
BANKI, K;MACEDA, J;PERL, A
人类嗜T细胞病毒（HTLV）相关的内源性序列，HRES-1，在人类基因组中的存在已被记录。HRES-1基因组基因座具有转录活性并含有开放阅读框。抗体232和233对合成肽pep 14 -24和pep 117 -127具有特异性，对应于HRES-1较长开放阅读框中两个不重叠的HTLV相关区域，识别H9人T细胞中相同的28-kDa蛋白。因此，HRES-1是一种能够表达蛋白质的人内源性逆转录病毒序列。HRES-1/p28定位于细胞质和核小体。HTLV-1特异性抗体与HRES-1肽反应，而抗体233与HTLV-1 gag p24蛋白交叉反应。HRES-1 pep 117 -127和HTLV-1gagp 24中存在的三个连续的高电荷氨基酸残基Arg-Arg-Glu可能是交叉反应表位的核心。对65例正常献血员和146例免疫性疾病患者进行了HRES-1肽pep 14 -24和pep 117 -127抗体检测。多发性硬化症（65例中的19例，29%）、进行性系统性硬化症（17例中的4例，23%）、系统性红斑狼疮（19例中的4例，21%）和干燥综合征（19例中的2例，10%）患者的血清含有比正常供体血清显著更高的HRES-1肽结合活性。艾滋病患者血清与HRES-1多肽无特异性结合。30例HRES-1血清阳性患者中有9例对HTLV-I gag p24呈免疫反应性。这些数据表明，HRES-1/p28可以作为自身抗原引发与HTLV-1 gag抗原交叉反应的自身抗体。
The presence of a human T-cell lymphotropic virus (HTLV)-related endogenous sequence, HRES-1, in the human genome has been documented. The HRES-1 genomic locus is transcriptionally active and contains open reading frames. Antibodies 232 and 233, specific for synthetic peptides pep14-24 and pep117-127, corresponding to two nonoverlapping HTLV-related regions in the longer open reading frame of HRES-1, recognize an identical 28-kDa protein in H9 human T cells. Thus, HRES-1 is a human endogenous retroviral sequence capable of protein expression. HRES-1/p28 is localized to the cytoplasm and nuclear bodies. While HTLV-I-specific antibodies react with HRES-1 peptides, antibody 233 cross-reacts with HTLV-I gag p24 protein. Three consecutive highly charged amino acid residues, Arg-Arg-Glu, present in both HRES-1 pep117-127 and HTLV-I gag p24 are likely to be the core of cross-reactive epitopes. The prevalence of antibodies to HRES-1 peptides pep14-24 and pep117-127 was determined in 65 normal blood donors and 146 patients with immunological disorders. Sera of patients with multiple sclerosis (19 out of 65, 29%), progressive systemic sclerosis (4 out of 17, 23%), systemic lupus erythematosus (4 out of 19, 21%), and Sjogren syndrome (2 out of 19, 10%) contained significantly higher HRES-1 peptide binding activity than sera of normal donors. Sera of patients with AIDS showed no specific binding to HRES-1 peptides. Nine of 30 HRES-1-seropositive patients showed immunoreactivity to HTLV-I gag p24. The data indicate that HRES-1/p28 may serve as an autoantigen eliciting autoantibodies cross-reactive with HTLV-I gag antigens.