cross-reactivity of herpesvirus-specific cd8 t cell lines toward allogeneic class i mhc molecules大herpesvirus-specific cd8 t细胞系对同种异体mhc分子类.pdf

Cross-Reactivity of Herpesvirus-Specific CD8 T Cell Lines Toward Allogeneic Class I MHC Molecules 1 ´ 2 ´ ` 1 2,3,4 2,3,4 Alexis Morice , Beatrice Charreau , Berangere Neveu , Sophie Brouard , Jean-Paul Soulillou , Marc Bonneville1, Elisabeth Houssaint1,5, Nicolas Degauque2,3,4* ´ ´ 1 UMR892, INSERM - Institut de Recherche Therapeutique de l’Universite de Nantes, Nantes, France, 2 UMR 643, INSERM, Nantes, France, 3 ITUN, CHU Nantes, Nantes, ´ ´ ´ ´ ´ France, 4 Faculte de Medecine, Universite de Nantes, Nantes, France, 5 Faculte des Sciences, Universite de Nantes, Nantes, France Abstract Although association between persistent viral infection and allograft rejection is well characterized, few examples of T-cell cross-reactivity between self-MHC/viral and allogeneic HLA molecules have been documented so far. We appraised in this study the alloreactivity of CD8 T cell lines specific for immunodominant epitopes from human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). CD8 T cell lines were generated after sorting with immunomagnetic beads coated with either pp65495–503/A*0201, BMLF1259–267/A*0201, or BZLF154–64/B*3501 multimeric complexes. Alloreactivity of the CD8 T cell lines against allogeneic class I MHC alleles was assessed by screening of (i) TNF-a production against COS-7 cells transfected with as many as 39 individual HLA class I-encoding cDNA, and (ii) cytotoxicity activity toward a large panel of HLA-typed EBV- transformed B lymphoblastoid cell lines. We identified several cross-reactive pp65/A*0201-spe