CROSS-REACTIVITY OF CYTOMEGALOVIRUS-SPECIFIC CD8+ T CELLS TO ALLO-MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I MOLECULES

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Abstract
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.