Mirano-Bascos Denise, Tary-Lehmann Magdalena, Landry Samuel J
Interdisciplinary Program in the Biomedical Sciences, Tulane University, New Orleans, LA 70112, USA.
Eur J Immunol. 2008 May;38(5):1231-7. doi: 10.1002/eji.200738011.
The development of an effective vaccine against HIV/AIDS has been hampered, in part, by a poor understanding of the rules governing helper T-cell epitope immunodominance. Studies in mice have shown that antigen structure modulates epitope immunodominance by affecting the processing and subsequent presentation of helper T-cell epitopes. Previous epitope mapping studies showed that the immunodominant helper T-cell epitopes in mice immunized with gp120 were found flanking flexible loops of the protein. In this report, we show that helper T-cell epitopes against gp120 in humans infected with HIV are also found flanking flexible loops. Immunodominant epitopes were found to be located primarily in the outer domain, an average of 12 residues C-terminal to flexible loops. In the less immunogenic inner domain, epitopes were found an average of five residues N-terminal to conserved regions of the protein, once again placing the epitopes C-terminal to flexible loops. These results show that antigen structure plays a significant role in the shaping of the helper T-cell response against HIV gp120 in humans. This relationship between antigen structure and helper T-cell epitope immunodominance may prove to be useful in the development of rationally designed vaccines against pathogens such as HIV.
开发一种有效的抗艾滋病毒/艾滋病疫苗受到了阻碍，部分原因是对辅助性T细胞表位免疫显性的调控规则了解不足。对小鼠的研究表明，抗原结构通过影响辅助性T细胞表位的加工及随后的呈递来调节表位免疫显性。先前的表位图谱研究表明，用gp120免疫的小鼠中，免疫显性辅助性T细胞表位位于该蛋白的柔性环两侧。在本报告中，我们表明，感染艾滋病毒的人类体内针对gp120的辅助性T细胞表位也位于柔性环两侧。发现免疫显性表位主要位于外部结构域，在柔性环C端平均12个残基处。在免疫原性较低的内部结构域中，表位位于该蛋白保守区域N端平均5个残基处，表位同样位于柔性环的C端。这些结果表明，抗原结构在塑造人类针对艾滋病毒gp120的辅助性T细胞反应中起着重要作用。抗原结构与辅助性T细胞表位免疫显性之间的这种关系可能在开发针对艾滋病毒等病原体的合理设计疫苗方面被证明是有用的。
