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International Immunology Advance Access originally published online on January 23, 2006
International Immunology 2006 18(3):435-444; 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

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

Mihyung Kim1,3, Hee-Bom Moon2, Kilhyoun Kim1 and Ki-Young Lee2

1 Division of Molecular Life Sciences and College of Pharmacy, Ewha Womans University, 11 Daehyundong, Seoul 120-750, 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 Present address: Research Laboratory, Anterogen Co., Ltd., Seoul 156-811, Korea

Correspondence to: K.-Y. Lee; E-mail: kiyounglee{at}amc.seoul.kr and K. Kim; E-mail: khyounk{at}ewha.ac.kr

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 Vß 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 Vß 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

Transmitting editor: E. Vivier


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