HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900162v1 183/4/2851    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Naumova, E. N. Articles by Naumov, Y. N. PubMed PubMed Citation Articles by Naumova, E. N. Articles by Naumov, Y. N.

Two Compensatory Pathways Maintain Long-Term Stability and Diversity in CD8 T Cell Memory Repertoires^1,2

Elena N. Naumova^*, Jack Gorski and Yuri N. Naumov^3,

^* Department of Public Health and Family Medicine, Tufts University School of Medicine, Boston, MA 02111; Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201; and Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by the National Institutes of Health Grant U19 AI062627.

² The contents of this publication are solely the responsibility of the authors and do not represent the official view of the National Institutes of Health.

³ Address correspondence and reprint requests to Dr. Yuri N. Naumov, Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655. E-mail address: yuri.naumov{at}umassmed.edu

⁴ Abbreviations used in this paper: RS, Arg₂Ser₃; GxY, Gly₂X₃Tyr₄; CDR3aa, CDR3 amino acid.

⁵ The online version of this article contains supplemental material.