title: Clonally related CD8+ T cells responsible for rapid population of both diffuse nasal-associated lymphoid tissue and lung after respiratory virus infection.
abstract: The immune system has evolved to use sophisticated mechanisms to recruit lymphocytes to sites of pathogen exposure. Trafficking pathways are precise. For example, lymphocytes that are primed by gut pathogens can, in some cases, be imprinted with CCR9 membrane receptors, which can influence migration to the small intestine. Currently, little is known about T cell trafficking to the upper respiratory tract or the relationship between effectors that migrate to the diffuse nasal-associated lymphoid tissue (d-NALT), the lower airways, and the lung. To determine whether a T cell primed by Ag from a respiratory pathogen is imprinted for exclusive trafficking to the upper or lower respiratory tract or whether descendents from that cell have the capacity to migrate to both sites, we inoculated mice by the intranasal route with Sendai virus and conducted single-cell-sequencing analyses of CD8(+) T lymphocytes responsive to a K(b)-restricted immunodominant peptide, FAPGNYPAL (Tet(+)). Cells from the d-NALT, lung airways (bronchoalveolar lavage), lung, and mediastinal lymph node were examined 10 d postinfection to determine TCR usage and clonal relationships. We discovered that 1) Tet(+) cells were heterogeneous but preferentially used TCR elements TRAV6, TRAV16, and TRBD1; 2) both N and C termini of Vα and Vβ TCR junctions frequently encompassed charged residues, perhaps facilitating TCR αβ pairing and interactions with a neutral target peptide; and 3) T cells in the d-NALT were often clonally related to cells in the lower respiratory tract.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Sherri L
authors.initials: SL
authors.lastname: Surman
authors.forename: Rajeev
authors.initials: R
authors.lastname: Rudraraju
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.forename: Pradyot
authors.initials: P
authors.lastname: Dash
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002465:Cell Movement / Q000276:immunology*; D002999:Clone Cells; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005260:Female; D006183:H-2 Antigens / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D016056:Immunodominant Epitopes / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D010253:Respirovirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D029082:Sendai virus / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D016056:Immunodominant Epitopes; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta