Impacts of avidity and specificity on the antiviral efficiency of HIV-1-specific CTL

被引:76
作者
Yang, OO
Sarkis, PTN
Trocha, A
Kalams, SA
Johnson, RP
Walker, BD
机构
[1] Univ Calif Los Angeles, Div Infect Dis, Ctr Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90095 USA
[3] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Partners AIDS Res Ctr, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Div Infect Dis, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, New England Reg Primate Ctr, Southborough, MA 01772 USA
[8] Harvard Univ, Sch Med, Div Aids, Southborough, MA 01772 USA
关键词
D O I
10.4049/jimmunol.171.7.3718
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Although CD8(+) CTLs are presumed to be an important mediator of protective immunity in HIV-1 infection, the factors that determine CTL antiviral efficiency are poorly understood. Two factors that have been proposed to influence CTL antiviral function are antigenic avidity and epitope specificity. In this study we evaluate these by examining the activity of HIV-1-specific CTL against acutely infected cells. The ability of CTL to kill infected cells is variable and depends more on epitope specificity than functional avidity within the range for the tested clones (50% of maximal killing, 50 pg/ml to 100 ng/ml); killing efficiency is similar for different clones recognizing the same epitope, despite their variation in avidity. When CTL clones are tested for their ability to suppress viral replication, similar results are observed. Inhibition is more dependent on epitope specificity than functional avidity among the tested clones (50% of maximal killing, 20 pg/ml to 20 ng/ml). Thus, CTL specificity can be an overriding factor in the ability of CTL to interact with HIV-1-infected cells, indicating that factors determining the process of epitope presentation on infected cells have a key influence on CTL efficiency. These results suggest that CTL specificity may have a pivotal role in the immunopathogenesis of infection, and that simple quantitative measures of CTL may be insufficient indicators of the CTL response to HIV-1.
引用
收藏
页码:3718 / 3724
页数:7
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