Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion

Nicole L La Gruta; William T Rothwell; Tania Cukalac; Natasha G Swan; Sophie A Valkenburg; Katherine Kedzierska; Paul G Thomas; Peter C Doherty; Stephen J Turner

Journal article

Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion

Nicole L La Gruta, William T Rothwell, Tania Cukalac, Natasha G Swan, Sophie A Valkenburg, Katherine Kedzierska, Paul G Thomas, Peter C Doherty, Stephen J Turner

JOURNAL OF CLINICAL INVESTIGATION | AMER SOC CLINICAL INVESTIGATION INC | Published : 2010

DOI: 10.1172/JCI41538

Abstract

CD8+ T cell responses to viral infection are characterized by the emergence of dominant and subdominant CTL populations. The immunodominance hierarchies of these populations are highly reproducible for any given spectrum of virus-induced peptide-MHCI complexes and are likely determined by multiple factors. Recent studies demonstrate a direct correlation between naive epitope-specific CD8+ T cell precursor (CTLp) frequency and the magnitude of the response after antigen challenge. Thus, the number of available precursors in the naive pool has emerged as a key predictor of immunodominance. In contrast to this, we report here no consistent relationship between CTLp frequency and the subsequent ..

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University of Melbourne Researchers

Stephen Turner Author Microbiology and Immunology

Peter Doherty Author Microbiology and Immunology

Katherine Kedzierska Author Microbiology and Immunology

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Grants

Awarded by National Health and Medical Research Council (NHMRC)

Awarded by NIH

Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Funding Acknowledgements

We thank D. Godfrey, F. Carbone, W. Heath, and K. Shortman for reagents and). Rossjohn for critical review of the manuscript. This work was supported by National Health and Medical Research Council (NHMRC) project grants AI454595 (to N.L. La Gruta and P.C. Doherty) and AI454312 (to K. Kedzierska), NHMRC Program grant (AI567122 to P.C. Doherty), NIH grants AI70251 (to P.C. Doherty) and AI065097 (to P.G. Thomas), NHMRC RD Wright Career Development Awards (to N.L. La Gruta and K. Kedzierska), a Pfizer Australia Research Fellowship (to S.J. Turner), an NHMRC Biomedical Postgraduate Scholarship (ID520643 to T. Cukalac), and an Australian-American Fulbright Postgraduate Scholarship (to W.T. Rothwell).