Cross-reactivity of herpesvirus-specific CD8 T cell lines toward allogeneic class I MHC molecules.
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 pp65(495-503)/A*0201, BMLF1(259-267)/A*0201, or BZLF1(54-64)/B*3501 multimeric complexes. Alloreactivity of the CD8 T cell lines against allogeneic class I MHC alleles was assessed by screening of (i) TNF-alpha 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-specific T cell lines toward allogeneic HLA-A*3001, A*3101, or A*3201. Moreover, we described here cross-recognition of HLA-Cw*0602 by BZLF1/B*3501-specific T cells. It is noteworthy that these alloreactive CD8 T cell lines showed efficient recognition of endothelial cells expressing the relevant HLA class I allele, with high level TNF-alpha production and cytotoxicity activity. Taken together, our data support the notion that herpes virus-specific T cells recognizing allo-HLA alleles may promote solid organ rejection.
Morice
Alexis
A
UMR892, INSERM-Institut de Recherche Thérapeutique de l'Université de Nantes, Nantes, France.
Charreau
Béatrice
B
Neveu
Bérangère
B
Brouard
Sophie
S
Soulillou
Jean-Paul
JP
Bonneville
Marc
M
Houssaint
Elisabeth
E
Degauque
Nicolas
N
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D003587:Cytomegalovirus / Q000276:immunology*; D042783:Endothelial Cells / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013045:Species Specificity
D000939:Epitopes; D006680:HLA Antigens