Barra C, Gournier H, Garcia Z, Marche P N, Jouvin-Marche E, Briand P, Fillipi P, Lemonnier F A
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Marseille, France.
J Immunol. 1993 May 1;150(9):3681-9.
DBA/2 (H-2d) HLA-B7 x human beta 2-microglobulin transgenic and DBA/2 nontransgenic mice stimulated by DBA/2 HLA-A3 x human beta 2-microglobulin transgenic mouse spleen cells developed potent H-2Kd restricted cytolytic responses with recognition of a peptide from the second domain of the HLA-A3 H chain. These H-2Kd-restricted responses obliterated, as a rule, cytolytic responses with direct recognition of the HLA-A3 molecules, even in HLA-B7 transgenic mice. These immunodominant H-2Kd-restricted responses could be abrogated in DBA/2 HLA-A24 mice because of cross-tolerance, the HLA-A3 derived-H-2Kd presented peptide being shared by several (including A24) HLA class I H chain allelic variants. Under such experimental circumstances, strong CTL responses with exclusive direct recognition of HLA-A3 molecules constantly developed. Further analysis of these responses in six DBA/2 HLA-A24 responder mice indicated that a large fraction of the mouse V beta and V alpha genes could be used to mount such CTL responses. Thus, by combining classical HLA class I transgenesis and selective destruction of H-2K and H-2D genes, it should be possible to derive useful strains of mice for the study of HLA class I-restricted CTL responses.
用DBA/2 HLA - A3×人β2 - 微球蛋白转基因小鼠脾细胞刺激的DBA/2（H - 2d）HLA - B7×人β2 - 微球蛋白转基因小鼠和DBA/2非转基因小鼠，产生了有效的H - 2Kd限制的细胞溶解反应，可识别来自HLA - A3重链第二结构域的一种肽。通常，这些H - 2Kd限制的反应消除了对HLA - A3分子的直接识别的细胞溶解反应，即使在HLA - B7转基因小鼠中也是如此。由于交叉耐受，在DBA/2 HLA - A24小鼠中这些免疫显性的H - 2Kd限制的反应可能被消除，因为HLA - A3衍生的 - H - 2Kd呈递的肽被几种（包括A24）HLA I类重链等位基因变体共享。在这种实验情况下，持续产生了对HLA - A3分子具有排他性直接识别的强烈CTL反应。对六只DBA/2 HLA - A24反应小鼠中这些反应的进一步分析表明，很大一部分小鼠Vβ和Vα基因可用于引发这种CTL反应。因此，通过结合经典的HLA I类转基因和H - 2K及H - 2D基因的选择性破坏，应该有可能获得用于研究HLA I类限制的CTL反应的有用小鼠品系。
