Cytomegalovirus-specific CD8+ T cells targeting different peptide/HLA combinations demonstrate varying T-cell receptor diversity

Abstract

Cytomegalovirus (CMV) infection and reactivation pose a serious threat for patients after haematopoietic stem cell transplantation. We have previously shown that CD8(+) T cells targeting different CMV epitopes correlate with protection at different threshold frequencies in those patients. To investigate if this may relate to a different quality of these cells here we analyse the T-cell receptor diversity of pp50 (245-253)/HLA-A*0101 specific CD8(+) T cells with that of CD8(+) T cells targeting various pp65 peptides. The results from this pilot study show differences in the breadth of the T-cell receptor usage of the different cell populations. We observe for the first time that the T-cell receptor Vβ CDR3 spectratypes used by CMV pp50 (245-253)/HLA-A*0101-specific CD8(+) T cells can reach higher numbers than those used by CD8(+) T cells targeting various pp65 peptides in our patient cohort. This merits further investigation into the effectiveness of the different CMV-specific T cells and their impact on immunosenescence, which is important to eventually define the most useful source of adoptive therapy and monitoring protocols for cytomegalovirus-specific immune responses.