The human cytomegalovirus (CMV) protein UL40 encodes a peptide that shares an identical sequence with a peptide found in the leader sequence many human leukocyte antigen (HLA)-C alleles. When complexed with HLA-E, the UL40-derived peptide can modulate NK cell functions via interactions with the CD94-NKG2 receptors. However the UL40-derived sequence can also be immunogenic, eliciting robust CD8+ T cell responses. In the setting of solid organ transplantation these T cells may not only be involved in antiviral immunity but also can potentially contribute to allograft rejection when the UL40 epitope is also present in allograft-encoded HLA. Here we assessed 15 bilateral lung transplant recipients (LTR) for the presence of HLA-E-restricted UL40-specific T cells by tetramer staining of peripheral blood mononuclear cells. UL40-specific T cells were observed in 7 LTR post-transplant however the magnitude of the response varied significantly between patients. Unlike in healthy CMV seropositive individuals, longitudinal analyses revealed that proportions of such T cells fluctuated markedly in LTR. Nine patients experienced low-grade acute cellular rejection, of which 6 also demonstrated UL40-specific T cells. Furthermore, the presence of UL40-specific CD8+ T cells in the blood was significantly associated with allograft dysfunction, which manifested as Bronchiolitis Obliterans Syndrome (BOS). Therefore, this study suggests that CMV antigens presented by HLA-E can represent an additional risk factor following lung transplantation.