This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Munitic, I. Articles by Rocha, B. PubMed PubMed Citation Articles by Munitic, I. Articles by Rocha, B.

 Previous Article  |  Next Article 

Journal of Virology, November 2009, p. 11795-11807, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01402-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Epitope Specificity and Relative Clonal Abundance Do Not Affect CD8 Differentiation Patterns during Lymphocytic Choriomeningitis Virus Infection

Ivana Munitic,^1,* Hélène Decaluwe,^2, César Evaristo,¹ Sara Lemos,¹ Myriam Wlodarczyk,³ Andrew Worth,⁵ Agnès Le Bon,^1, Liisa K. Selin,³ Yves Rivière,⁴ James P. Di Santo,² Persephone Borrow,⁵ and Benedita Rocha^1*

INSERM, U591, Faculté de Médecine Descartes Paris 5, Paris, France,¹ INSERM, U668, Unité des Cytokines et Développement Lymphoïde, Institut Pasteur, Paris, France,² Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605,³ Laboratoire d'Immunopathologie Virale, CNRS URA3015, Paris, France,⁴ Nuffield Department of Clinical Medicine, University of Oxford, The Jenner Institute, Compton, Newbury, Berkshire RG20 7NN, United Kingdom⁵

Received 8 July 2009/ Accepted 24 August 2009

To evaluate the impact of immunodominance on CD8 T-cell properties, we compared the functional properties of dominant and subdominant populations in the response to lymphocytic choriomeningitis virus (LCMV). To improve functional discrimination, in addition to the usual tests of phenotype and function, we used a sensitive technique that allows the screening of all CD8 effector genes simultaneously in single cells. Surprisingly, these methods failed to reveal a major impact of clonal dominance in CD8 properties throughout the response. Aiming to increase clonal dominance, we examined high-frequency transferred P14 T-cell receptor transgenic (TCR Tg) cells. Under these conditions LCMV is cleared faster, and accordingly we found an accelerated response. However, when Tg and endogenous cells were studied in the same mice, where they should be subjected to the same antigen load, they showed overlapping properties, and the presence of P14 cells did not modify endogenous responses to other LCMV epitopes or a perturbed immunodominance hierarchy in the memory phase. Using allotype-labeled Tg cells, we found that during acute infection up to 80% downregulated their TCR and were undetectable by tetramer binding, and that tetramer-negative and tetramer-positive cells had very different features. Since Tg cells are not available to evaluate immune responses in humans and, in many cases, are not available from the mouse, the tetramer-based evaluation of early immune responses in most situations of high viremia may be incomplete and biased.

---

* Corresponding author. Mailing address for B. Rocha: INSERM, U591, Faculté de Médecine Descartes Paris 5, Paris, France. Phone: (33) 1 40 61 53 65. Fax: (33) 1 40 61 55 80. E-mail: benedita.rocha{at}inserm.fr. Mailing address for I. Munitic: Laboratory of Immune Cell Biology, NCI, NIH, Bethesda, MD. Phone: (301) 594-7908. Fax: (301) 402-4844. E-mail: munitic{at}mail.nih.gov

Published ahead of print on 2 September 2009.

These authors contributed equally to this work.

Present address: INSERM U567, Institut Cochin, Paris, France.

---

Journal of Virology, November 2009, p. 11795-11807, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01402-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.