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International Immunology Advance Access published online on January 23, 2006
International Immunology, doi:10.1093/intimm/dxh383
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received July 28, 2005
Accepted December 12, 2005

Article

Antigen dose governs the shaping of CTL repertoires in vitro and in vivo

Mihyung Kim 1, Hee-Bom Moon 2, Kilhyoun Kim 3, and Ki-Young Lee 2 *

1 Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, 11 Daehyundong, Seoul 120-750, Korea; Present address: Research Laboratory, Anterogen Co., Ltd., Seoul 156-811, Korea
2 Division of Allergy, Asan Medical Center and Asan Institute for Life Science, University of Ulsan College of Medicine, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, Korea
3 Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, 11 Daehyundong, Seoul 120-750, Korea

* To whom correspondence should be addressed.
Ki-Young Lee, E-mail: khyounk{at}ewha.ac.kr


  Abstract

Although it is well established that antigen dose plays an important role in determining the quality of T cells induced in vitro, it has not well been determined whether antigen dose also affects T cell repertoires induced in vivo. This study demonstrates that variation of antigen doses in vivo as well as in vitro induce structurally and functionally different T cell repertoires. CTLs generated in vitro with a low antigen dose showed much higher T cell responsiveness than CTLs generated with a high antigen dose, and the two CTL populations employed different TCR V{beta} chains. This is most likely due to repertoire selection based on TCR affinity. The secondary in vivo responses with a high or low dose of antigen following the primary response raised with the same dose resulted in a reversed dominance pattern of two particular TCR V{beta} phenotypes. TCR affinity of these two T cell populations appeared different, suggesting avidity selection based on antigen availability. Indeed, they required a distinct level of antigen for maximal cytolytic function, implying a different functional avidity. These results suggest that antigen-specific T cell repertoire is substantially affected by the antigen dose employed in vivo as well as in vitro.

Keywords: antigen dose; CTL; repertoire development; T cell avidity.
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