Two compensatory pathways maintain long-term stability and diversity in CD8 T cell memory repertoires.
The time-dependent changes of human memory T cell repertoires are still poorly understood. We define a T cell memory repertoire as the pool of clonotypic lineages participating in a recall response to the influenza M1(58-66) epitope. In HLA-A2 individuals, this response predominantly uses BV19 chains with Arg-Ser (RS) in the CDR3 loop. We previously showed that the repertoire is polyclonal with a large fraction of clonotype that are only observed once. In this study, we perform longitudinal analyses of memory repertoires in three middle-aged individuals at times that spanned from 7 to 10 years. In these individuals, who are well into thymic involution, a substantial number of clonotypes were stable, e.g., detected at two times. The shape of the repertoire was stable over time as reflected by a number of repertoire characteristics, including singletons, i.e., the fraction of clonotypes observed only once, and repertoire diversity. However, the RS-clonotype subset showed a significant decline in the fraction of singletons and in clonotypic diversity. Thus, repertoire structure is maintained over time by a recruitment of non-RS-clonotypes and a shift of existing RS-clonotypes into higher frequencies. The recruitment of new clonotypes into the low-frequency component of the repertoire implies a role for these clonotypes.
Naumova
Elena N
EN
Department of Public Health and Family Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.
Gorski
Jack
J
Naumov
Yuri N
YN
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology*; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000276:immunology; D017124:Conserved Sequence; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology*; D013045:Species Specificity; D014763:Viral Matrix Proteins / Q000276:immunology
D022801:Complementarity Determining Regions; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins