Competition for antigen at the level of the APC is a major determinant of immunodominance during memory inflation in murine cytomegalovirus infection.

Authors

Lila A Farrington, Oregon Health Science UniversityFollow
Tameka A Smith, Oregon Health Science University
Finn Grey, University of Edinburgh
Ann B Hill, Oregon Health Science UniversityFollow
Christopher M. Snyder, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

4-1-2013

Comments

This article has been peer reviewed. It is the authors' final version prior to publication in The Journal of immunology

Volume 190, Issue 7, April 2013, Pages 3410-6.

The published version is available at DOI: 10.4049/jimmunol.1203151. Copyright © The American Association of Immunologists, Inc.

Abstract

The unique ability of CMV to drive the expansion of virus-specific T cell populations during the course of a lifelong, persistent infection has generated interest in the virus as a potential vaccine strategy. When designing CMV-based vaccine vectors to direct immune responses against HIV or tumor Ags, it becomes important to understand how and why certain CMV-specific populations are chosen to inflate over time. To investigate this, we designed recombinant murine CMVs (MCMVs) encoding a SIINFEKL-enhanced GFP fusion protein under the control of endogenous immediate early promoters. When mice were infected with these viruses, T cells specific for the SIINFEKL epitope inflated and profoundly dominated T cells specific for nonrecombinant (i.e., MCMV-derived) Ags. Moreover, when the virus encoded SIINFEKL, T cells specific for nonrecombinant Ags displayed a phenotype indicative of less frequent exposure to Ag. The immunodominance of SIINFEKL-specific T cells could not be altered by decreasing the number of SIINFEKL-specific cells available to respond, or by increasing the number of cells specific for endogenous MCMV Ags. In contrast, coinfection with viruses expressing and lacking SIINFEKL enabled coinflation of T cells specific for both SIINFEKL and nonrecombinant Ags. Because coinfection allows presentation of SIINFEKL and MCMV-derived Ags by different cells within the same animal, these data reveal that competition for, or availability of, Ag at the level of the APC determines the composition of the inflationary response to MCMV. SIINFEKL's strong affinity for H-2K(b), as well as its early and abundant expression, may provide this epitope's competitive advantage.

Recommended Citation

Farrington, Lila A; Smith, Tameka A; Grey, Finn; Hill, Ann B; and Snyder, Christopher M., "Competition for antigen at the level of the APC is a major determinant of immunodominance during memory inflation in murine cytomegalovirus infection." (2013). Department of Microbiology and Immunology Faculty Papers. Paper 68.
https://jdc.jefferson.edu/mifp/68

PubMed ID

23455500