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Quantification of Repertoire Diversity of Influenza-Specific Epitopes with Predominant Public or Private TCR Usage¹

Katherine Kedzierska^*, E. Bridie Day^*, Jing Pi^*, Stephen B. Heard, Peter C. Doherty^*, Stephen J. Turner^* and Stanley Perlman^2,

^* Department of Microbiology and Immunology, The University of Melbourne, Parkeville, Victoria, Australia; Department of Biology, University of New Brunswick, Fredericton, New Brunswick, Canada; and Department of Microbiology, University of Iowa, Iowa City, IA 52242

The H-2D^b-restricted CD8 T cell immune response to influenza A is directed at two well-described epitopes, nucleoprotein 366 (NP366) and acid polymerase 224 (PA224). The responses to the two epitopes are very different. The epitope NP366-specific response is dominated by TCR clonotypes that are public (shared by most mice), whereas the epitope PA224-specific response is private (unique within each infected animal). In addition to being public, the NP366-specific response is dominated by a few clonotypes, when T cell clonotypes expressing the V8.3 element are analyzed. Herein, we show that this response is similarly public when the NP366⁺V4⁺ CD8 T cell response is analyzed. Furthermore, to determine whether these features resulted in differences in total TCR diversity in the NP366⁺ and PA224⁺ responses, we quantified the number of different CD8 T clonotypes responding to each epitope. We calculated that 50–550 clonotypes recognized each epitope in individual mice. Thus, although the character of the response to the two epitopes appeared to be different (private and diverse vs public and dominated by a few clonotypes), similar numbers of precursor cells responded to both epitopes and this number was of similar magnitude to that previously reported for other viral CD8 T cell epitopes. Therefore, even in CD8 T cell responses that appear to be oligoclonotypic, the total response is highly diverse.

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 a Burnet Fellowship (to P.C.D.), a Peter Doherty Postdoctoral Fellowship (to K.K.), an R. D. Wright Fellowship (to S.J.T.), Dora Lush Postgraduate Scholarship (to E.B.D.) from the Australian National Health and Medical Research Council, by a University of Melbourne Early Career Researcher grant (to S.J.T.), by Science, Technology and Innovation funds from the Government of Victoria, Australia, by the National Institutes of Health (NS036592; to S.P.), and by a Natural Sciences and Engineering Research Council (Canada) Discovery Grant (to S.B.H.).

² Address correspondence and reprint requests to Dr. Stanley Perlman, Department of Microbiology, University of Iowa, BSB 3-712, Iowa City, IA 52242. E-mail address: stanley-perlman{at}uiowa.edu

³ Abbreviations used in this paper: NP, nucleoprotein; PA, acid polymerase; LCMV, lymphocytic choriomeningitis virus; MHV, mouse hepatitis virus.

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