MHC class Ib-restricted CD8 T cells differ in dependence on CD4 T cell help and CD28 costimulation over the course of mouse polyomavirus infection

Amelia R. Hofstetter, Mandy L. Ford, Lucy C. Sullivan, Jarad J. Wilson, Annette Hadley, Andrew G. Brooks, Aron E. Lukacher

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We recently identified a protective MHC class Ib-restricted CD8 T cell response to infection with mouse polyomavirus. These CD8 T cells recognize a peptide from aa 139-147 of the VP2 viral capsid protein bound to the nonpolymorphic H-2Q9 molecule, a member of the Qa-2 family of β 2m-associated MHC class Ib molecules. Q9:VP2.139-specific CD8 T cells exhibit an unusual inflationary response characterized by a gradual expansion over 3 mo followed by a stable maintenance phase. We previously demonstrated that Q9:VP2.139-specific CD8 T cells are dependent on Ag for expansion, but not for long-term maintenance. In this study, we tested the hypothesis that the expansion and maintenance components of the Q9:VP2.139-specific T cell response are differentially dependent on CD4 T cell help and CD28 costimulation. Depletion of CD4 + cells and CD28/CD40L blockade impaired expansion of Q9:VP2.139-specific CD8 T cells, and intrinsic CD28 signaling was sufficient for expansion. In contrast, CD4 T cell insufficiency, but not CD28/CD40L blockade, resulted in a decline in frequency of Q9:VP2.139-specific CD8 T cells during the maintenance phase. These results indicate that the Q9:VP2.139-specific CD8 T cell response to mouse polyomavirus infection depends on CD4 T cell help and CD28 costimulation for inflationary expansion, but only on CD4 T cell help for maintenance.

Original languageEnglish (US)
Pages (from-to)3071-3079
Number of pages9
JournalJournal of Immunology
Volume188
Issue number7
DOIs
StatePublished - Apr 1 2012

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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