T Cell Receptor alpha beta Diversity Inversely Correlates with Pathogen-Specific Antibody Levels in Human Cytomegalovirus Infection

• Published in: Science translational medicine 2012-04, Vol.4 (128), p.128ra42-128ra42
• Main Authors: Wang, G C, Dash, P, McCullers, JA, Doherty, P C, Thomas, P G
• Format: Article
• Language: English
• Subjects: Antibodies; CD8 antigen; Human cytomegalovirus; Infection; Lymphocytes T; Mortality; Mutation; Probes; T-cell receptor; Translation
• ISSN: 1946-6234
• DOI: 10.1126/scitranslmed.3003647

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 by counteracting escape mutations, selecting high-avidity T cells, and providing T cell specificities with comprehensive functional characteristics. However, evidence that TCR diversity is important for the successful control of human infections is limited. A single-cell strategy for the clonotypic analysis of human CD8 super(+) TCR alpha beta repertoires was used to probe the diversity and magnitude of individual human cytomegalovirus (CMV)-specific CD8 super(+) T cells recovered directly ex vivo. We found that CD8 super(+) TCR alpha beta repertoire diversity, but not the size of the CD8 super(+) 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, our findings indicate that CD8 super(+) T cell diversity may be more important than T cell abundance in limiting the negative consequences of CMV persistence, demonstrate high prevalence of both TCR alpha and TCR beta public motif usage, and suggest that a highly diverse TCR alpha beta repertoire may be an important benchmark and target in the success of immunotherapeutic strategies.