Acierno Paula M, Newton Danforth A, Brown Edwin A, Maes Lou Anne, Baatz John E, Gattoni-Celli Sebastiano
Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
J Transl Med. 2003 Aug 14;1(1):3. doi: 10.1186/1479-5876-1-3.
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.
甲型流感病毒的基质蛋白与人免疫缺陷病毒（HIV）的基质蛋白和衣壳蛋白具有显著的结构相似性，这可能具有进化和生物学意义。这些相似性使我们推测，在HLA - A2限制的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的HLA - A2 +供体淋巴细胞中FLU/GAG免疫交叉反应性的存在和程度，以检验这两个表位具有交叉反应性的假设。此外，通过比较与TCR - β可变区相对应的淋巴细胞衍生cDNA序列，研究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会导致相同T细胞克隆型的扩增。结果：在此，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，在体外刺激来自HIV血清阳性或血清阴性的HLA - A2 +供体的外周血单核细胞（PBMC）后，FLU - M1:58 - 66和HIV - 1 p17 GAG:77 - 85表位之间存在交叉反应性的证据。结论：这些结果表明，在接种流感疫苗的HIV感染和未感染供体中，针对流感病毒基质蛋白的免疫可能会引发针对HLA - A2限制的HIV gag表位的特异性免疫反应。
