Cytomegalovirus (CMV) causes significant morbidity and mortality in patients after haematopoietic
stem cell transplantation (HSCT). Due to limitations of current
antiviral therapies, alternative approaches, involving transfer of donor-derived CMV-specific CD8(+) T cells, have been considered. Levels of such cells correlating with protection against CMV
infection and disease have only been reported in patients expressing
HLA-A*0201 and
HLA-B*0702. This is despite an increasing number of reports describing cells targeting CMV
peptides presented by other human leucocyte
antigens (HLAs). Considering several frequent HLA alleles, our findings suggest that
HLA-A*2402/pp65 (341-349)- and
HLA-B*3501/pp65 (123-131)-specific CD8(+) T cells correlate with protection from CMV reactivation at significantly lower cell levels than
HLA-A*0101/pp50 (245-253)- and
HLA-A*0201/pp65 (495-503)-specific CD8(+) T cells, both in HSCT recipients post-transplant and in healthy CMV seropositive volunteers. This may result from a differing efficiency of the responses restricted by the two sets of HLA alleles. These findings add to the knowledge of immunodominance and differences in antigen processing that are coordinated in individuals with different HLA alleles and have direct implications for
therapy and monitoring in patients.