Role of α3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs
Role of α3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs
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DOI：
10.1093/intimm/dxm111
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发表时间：
2007-12-01
影响因子：
4.4
通讯作者：
Berzofsky，Jay A.
中科院分区：
文献类型：
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作者：
Belyakov，Igor M.;Kozlowski，Steven;Berzofsky，Jay A.
CD 8可作为CTL表面的辅助分子或辅助受体。作为共受体，CD 8可以结合与TCR相同的MHC I类分子的α3结构域，以促进TCR信号传导。为了评价MHC Ⅰ类分子α3区在CD 8 +CTL活化中的作用，我们制备了一个可溶性227突变体H-2Dd，α3区有一个点突变（Glu 227 →Lys）。通过表位特异性CD 8 +CTL细胞系产生IFN-γ的能力测定，227突变型I类肽复合物不能有效激活H-2Dd限制性CD 8 T细胞。然而，在另一种具有正常α3结构域的MHC I类分子（H-2Kb）（其不能呈递肽）存在下，227种突变的I类肽复合物可以诱导CD 8 +CTL的活化。因此，为了激活CD 8 +CTL，MHC I类的α3结构域不必与MHC I类的α1和α2结构域位于同一分子上。低亲合力的CD 8 +CTL细胞系对H-2Kb分子存在下的227突变I类肽复合物刺激的敏感性显著降低。因此，低亲合力CTL可能不能利用CD 8和非呈递I类MHC分子的α3结构域之间的相互作用，这可能是因为TCR-MHC相互作用的停留时间较短。
CD8 can serve as a co-receptor or accessory molecule on the surface of CTL. As a co-receptor, CD8 can bind to the α3 domain of the same MHC class I molecules as the TCR to facilitate TCR signaling. To evaluate the role of the MHC class I molecule α3 domain in the activation of CD8+CTL, we have produced a soluble 227 mutant of H-2Dd, with a point mutation in the α3 domain (Glu227→Lys). 227 mutant class I–peptide complexes were not able to effectively activate H-2Dd-restricted CD8 T cellsin vitro, as measured by IFN-γ production by an epitope-specific CD8+CTL line. However, the 227 mutant class I–peptide complexes in the presence of another MHC class I molecule (H-2Kb) (that cannot present the peptide) with a normal α3 domain can induce the activation of CD8+CTL. Therefore, in order to activate CD8+CTL, the α3 domain of MHC class I does not have to be located on the same molecule with the α1 and α2 domains of MHC class I. A low-avidity CD8+CTL line was significantly less sensitive to stimulation by the 227 mutant class I–peptide complexes in the presence of the H-2Kbmolecule. Thus, low-avidity CTL may not be able to take advantage of the interaction between CD8 and the α3 domain of non-presenting class I MHC molecules, perhaps because of a shorter dwell time for the TCR–MHC interaction.