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J Immunol. 2016 Oct 15;197(8):3214-3224. Epub 2016 Sep 2.

Circulating Memory CD4+ T Cells Target Conserved Epitopes of Rhinovirus Capsid Proteins and Respond Rapidly to Experimental Infection in Humans.

Author information

1
Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908.
2
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101.
3
Department of Pediatrics, University of Virginia Health System, Charlottesville, VA 22908; and.
4
Indoor Biotechnologies Inc., Charlottesville, VA 22903.
5
Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908; jaw4m@virginia.edu.

Abstract

Rhinovirus (RV) is a major cause of common cold and an important trigger of acute episodes of chronic lung diseases. Antigenic variation across the numerous RV strains results in frequent infections and a lack of durable cross-protection. Because the nature of human CD4+ T cells that target RV is largely unknown, T cell epitopes of RV capsid proteins were analyzed, and cognate T cells were characterized in healthy subjects and those infected by intranasal challenge. Peptide epitopes of the RV-A16 capsid proteins VP1 and VP2 were identified by peptide/MHC class II tetramer-guided epitope mapping, validated by direct ex vivo enumeration, and interrogated using a variety of in silico methods. Among noninfected subjects, those circulating RV-A16-specific CD4+ T cells detected at the highest frequencies targeted 10 unique epitopes that bound to diverse HLA-DR molecules. T cell epitopes localized to conserved molecular regions of biological significance to the virus were enriched for HLA class I and II binding motifs, and constituted both species-specific (RV-A) and pan-species (RV-A, -B, and -C) varieties. Circulating epitope-specific T cells comprised both memory Th1 and T follicular helper cells, and were rapidly expanded and activated after intranasal challenge with RV-A16. Cross-reactivity was evidenced by identification of a common *0401-restricted epitope for RV-A16 and RV-A39 by tetramer-guided epitope mapping and the ability for RV-A16-specific Th1 cells to proliferate in response to their RV-A39 peptide counterpart. The preferential persistence of high-frequency RV-specific memory Th1 cells that recognize a limited set of conserved epitopes likely arises from iterative priming by previous exposures to different RV strains.

PMID:
27591323
PMCID:
PMC5101128
DOI:
10.4049/jimmunol.1600663
[Indexed for MEDLINE]
Free PMC Article

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