Inverse relationship between T-cell receptor αβ repertoire diversity and pathogen-specific antibody levels in human cytomegalovirus infection (105.51)

Abstract

Abstract A diverse T-cell receptor (TCR) repertoire capable of recognizing a broad range of antigenic peptides is thought to be central to effective pathogen-specific immunity, but evidence that TCR diversity is important for the successful control of human infections is limited. A novel, single-cell strategy for the clonotypic analysis of human CD8+ TCRαβ repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8+ T-cells recovered directly ex vivo. We found that CD8+ TCRαβ repertoire diversity, but not the size of the CD8+ T-cell response, was inversely related to circulating CMV-specific antibody levels, a measure that has been correlated epidemiologically with differential mortality risks and found here to be higher in persons with detectable (versus undetectable) CMV viral loads. Overall, these findings indicate that CD8+ T-cell diversity may be more important than T-cell abundance in limiting the negative consequences of CMV persistence, and provides insights into the selection of TCRαβ public motifs in a life-long virus infection.