Cross-reactivity between HLA-A2-restricted FLU-M1:58-66 and HIV p17 GAG:77-85 epitopes in HIV-infected and uninfected individuals.
Cross-reactivity between HLA-A2-restricted FLU-M1:58-66 and HIV p17 GAG:77-85 epitopes in HIV-infected and uninfected individuals.
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DOI：
10.1186/1479-5876-1-3
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发表时间：
2003-08-14
影响因子：
7.4
通讯作者：
Gattoni-Celli, Sebastiano
中科院分区：
文献类型：
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作者：
Acierno, Paula M;Newton, Danforth A;Gattoni-Celli, Sebastiano
背景技术背景：甲型流感病毒的基质蛋白和人类免疫缺陷病毒（HIV）的基质和衣壳蛋白具有惊人的结构相似性，这可能具有进化和生物学意义。这些相似性使我们假设HLA-A2限制性FLU-M1：58-66和HIV-1 p17 GAG：77-85表位之间存在交叉反应性。方法：通过细胞毒性试验和四聚体分析确定HIV血清阳性和血清阴性HLA-A2+供体淋巴细胞中FLU/GAG免疫交叉反应性的存在和程度，检验这两个表位具有交叉反应性的假设。此外，通过比较对应于TCR-β可变区的淋巴细胞衍生的cDNA序列，研究了HIV血清阳性和血清阴性供体中FLU/GAG交叉反应性的分子基础，以确定用任一肽刺激淋巴细胞是否导致相同T细胞克隆型的扩增。研究结果：在这里，我们报告了通过细胞毒性试验、四聚体分析和分子克隆分型确定的体外刺激来自HIV血清阳性或血清阴性HLA-A2+供体的PBMC后FLU-M1：58-66和HIV-1 p17 GAG：77-85表位之间交叉反应性的证据。结论：这些结果表明，对流感病毒基质蛋白的免疫力可能会在接种流感疫苗的HIV感染和未感染供体中驱动对HLA-A2限制性HIV gag表位的特异性免疫应答。
BACKGROUND: The matrix protein of the influenza A virus and the matrix and capsid proteins of the human immunodeficiency virus (HIV) share striking structural similarities which may have evolutionary and biological significance. These similarities led us to hypothesize the existence of cross-reactivity between HLA-A2-restricted FLU-M1:58-66 and HIV-1 p17 GAG:77-85 epitopes. METHODS: The hypothesis that these two epitopes are cross-reactive was tested by determining the presence and extent of FLU/GAG immune cross-reactivity in lymphocytes from HIV-seropositive and seronegative HLA-A2+ donors by cytotoxicity assays and tetramer analyses. Moreover, the molecular basis for FLU/GAG cross-reactivity in HIV-seropositive and seronegative donors was studied by comparing lymphocyte-derived cDNA sequences corresponding to the TCR-beta variable regions, in order to determine whether stimulation of lymphocytes with either peptide results in the expansion of identical T-cell clonotypes. RESULTS: Here, we report evidence of cross-reactivity between FLU-M1:58-66 and HIV-1 p17 GAG:77-85 epitopes following in vitro stimulation of PBMC derived from either HIV-seropositive or seronegative HLA-A2+ donors as determined by cytotoxicity assays, tetramer analyses, and molecular clonotyping. CONCLUSION: These results suggest that immunity to the matrix protein of the influenza virus may drive a specific immune response to an HLA-A2-restricted HIV gag epitope in HIV-infected and uninfected donors vaccinated against influenza.