Circulating Memory CD4+ T Cells Target Conserved Epitopes of Rhinovirus Capsid Proteins and Respond Rapidly to Experimental Infection in Humans.
Lyndsey M MuehlingDuy T MaiWilliam W KwokPeter W HeymannAnna PomésJudith A WoodfolkPublished in: Journal of immunology (Baltimore, Md. : 1950) (2016)
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.
Keyphrases
- mycobacterium tuberculosis
- high frequency
- induced apoptosis
- escherichia coli
- cell cycle arrest
- endothelial cells
- magnetic resonance
- high resolution
- dendritic cells
- mass spectrometry
- regulatory t cells
- monoclonal antibody
- liver failure
- single molecule
- drug induced
- high density
- molecular docking
- mechanical ventilation
- cancer therapy
- contrast enhanced
- genetic diversity
- pi k akt