Meddows-Taylor Stephen, Papathanasopoulos Maria A, Kuhn Louise, Meyers Tammy M, Tiemessen Caroline T
AIDS Virus Research Unit, National Institute for Communicable Diseases, Private Bag X4, Sandringham, 2131, Johannesburg, South Africa.
Virus Genes. 2004 Apr;28(3):311-8. doi: 10.1023/b:viru.0000025788.85010.bd.
Although human immunodeficiency virus type 1 (HIV-1) specific CD4 T-helper cells are vital in mediating antiviral defence, little is known concerning the influence of HIV-1 antigenic variation on CD4 T-cell responses. In this study, the amino acid sequences of 5 synthetic HIV-1 envelope peptides used for in vitro stimulation (T2, P18 MN, P18 IIIB, T1 and TH4.1) were compared to the corresponding amino acid sequences of the gp 160 region of viruses isolated from HIV-1 infected children to determine whether variation in the envelope region of HIV-1 was associated with the ability to detect Env-specific T-helper cell responses. Although the T2 region appeared to offer some evidence as to the role antigenic variation may have played in class II-restricted CD4 T-cell responses between those children who showed a detectable Env-stimulated T-helper cell response and those who did not, the other regions studied showed no evidence of being more conserved among those children who showed detectable responses. The combined amino acid variation across the specific peptide regions studied was not associated with peripheral levels of HIV-1, nor did the degree of amino acid variation dictate the clinical category into which the children had been classified, although there was a tendency towards HIV-1 isolates from the younger children showing a greater degree of amino acid variation than isolates from the older children. These results suggest that HIV-1 specific CD4 responses may be somewhat tolerant of viral variation, although further studies are required to fully elucidate the effect of antigenic variation on immune recognition.
虽然1型人类免疫缺陷病毒(HIV-1)特异性CD4辅助性T细胞在介导抗病毒防御中至关重要,但关于HIV-1抗原变异对CD4 T细胞反应的影响却知之甚少。在本研究中,将用于体外刺激的5种合成HIV-1包膜肽(T2、P18 MN、P18 IIIB、T1和TH4.1)的氨基酸序列与从HIV-1感染儿童中分离出的病毒gp160区域的相应氨基酸序列进行比较,以确定HIV-1包膜区域的变异是否与检测Env特异性辅助性T细胞反应的能力相关。尽管T2区域似乎为抗原变异在显示可检测到的Env刺激辅助性T细胞反应的儿童和未显示该反应的儿童之间的II类限制性CD4 T细胞反应中可能发挥的作用提供了一些证据,但所研究的其他区域在显示可检测反应的儿童中没有显示出更保守的证据。在所研究的特定肽区域的氨基酸变异组合与HIV-1的外周水平无关,氨基酸变异程度也不能决定儿童被分类的临床类别,尽管有这样一种趋势,即较年幼儿童的HIV-1分离株比年长儿童的分离株显示出更大程度的氨基酸变异。这些结果表明,HIV-1特异性CD4反应可能对病毒变异有一定耐受性,尽管需要进一步研究来充分阐明抗原变异对免疫识别的影响。