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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900283v1 183/2/1013    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 Elnekave, M. Articles by Hovav, A.-H. PubMed PubMed Citation Articles by Elnekave, M. Articles by Hovav, A.-H.

A Matter of Timing: Unsynchronized Antigen Expression and Antigen Presentation Diminish Secondary T Cell Responses¹

Mazal Elnekave^*, Maytal Bivas-Benita, Geoffrey O. Gillard, Piya Sircar and Avi-Hai Hovav^2,*

^* Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel; and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115

Despite the low and short expression of secondary Ag, prime-boost immunizations using homologous or heterologous vectors are capable of amplifying memory CD8⁺ T cells. This is mainly attributed to the rapid presentation of Ag by APCs and the high proliferative capacity of memory CD8⁺ T cells. Nevertheless, certain viruses and vectors often require prolonged Ag presentation for optimal T cell priming, and the influence of such a prolonged presentation during secondary immune induction is not clear. To address this issue, we primed and boosted mice intradermally (i.d.) with plasmid DNA that was recently reported to require prolonged Ag presentation for maximal CD8⁺ T cell priming. Although functional memory CD8⁺ T cells were present in the mice after i.d. priming, the secondary CD8⁺ T cell response elicited was limited and reached a similar level of that observed during priming. The initial levels of secondary Ag expressed in the boosted mice were sufficient to prime CD8⁺ T cell response in naive hosts, suggesting that lower Ag load alone does not explain the limited secondary immune responses observed. Removal of the injection site 5 or 10 days after i.d. boosting immunization resulted in diminished Ag presentation and no expansion of memory CD8⁺ T cells. In fact, Ag-presenting activity following boost occurred mainly two weeks postimmunization, a time when the Ag was no longer expressed in situ. These findings suggest that when the boosting vector triggers prolonged Ag presentation, the lack of synchronicity between Ag accessibility and Ag presentation limits secondary immune responses.

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 supported by Marie Curie International Reintegration Grant 230932 and Bruno Goldberg Grant 036-5055.

² Address correspondence and reprint requests to Avi-Hai Hovav, Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, P.O. Box 122722, Jerusalem 91120, Israel. E-mail address: avihaih{at}ekmd.huji.ac.il

³ Abbreviations used in this paper: i.d., intradermal(ly); DC, dendritic cell; LN, lymph node; rAd, recombinant adenovirus.

⁴ The online version of this article contains supplemental material.