Cross-reactivity of cytomegalovirus-specific CD8+ T cells to allo-major histocompatibility complex class I molecules

BACKGROUND: In transplantation settings, cytomegalovirus (CMV) infection is a common complication. CMV infection is associated with a higher incidence of graft rejection in solid organ transplantation and graft-versus-host disease in bone marrow transplantation. The underlying mechanism of this association could be the generation of CMV-specific CD8 T cells capable of cross-reacting with alloantigens present on graft and host, respectively. METHODS: Whereas as to date, no direct ex vivo analysis can be performed of the CD8 T-cell repertoire directed at allo-major histocompatibility complex (MHC) class I molecules, virus-specific cells can be readily enumerated by use of MHC-peptide tetrameric complexes. In this study, the authors used this technique to analyze potential overlapping CD8 T-cell repertoires between self-MHC-viral peptide and allo-MHC complexes by stimulating CMV-specific CD8 T cells with alloantigens. RESULTS.: The authors found that CMV-specific CD8 T cells are activated and proliferate on stimulation with alloantigens. CONCLUSIONS: Although these cells are cytotoxic against CMV-peptide pulsed target cells, no cytotoxicity of CMV-specific cells to alloantigens could be detected, inferring that there are other mechanisms of graft damage by alloantigen-stimulated virus-specific CTL.