title: The functional CD8 T cell memory recall repertoire responding to the influenza A M1(58-66) epitope is polyclonal and shows a complex clonotype distribution.
abstract: The CD8 memory T cell repertoire to the influenza A derived M1(58-66) epitope shows a restricted V genes and CDR3 sequences usage. The repertoire is highly polyclonal and the clonotype distribution has been described as consisting of two components, one showing a power law-like distribution and the other composed of a few clonotypes with a very high relative frequency. The question is whether the complex repertoire defined by its ability to flourish in a short term recall culture corresponded to functional cells. Here we show that there is a relation between expression of the degranulation marker CD107 and cytotoxicity or IFN-γ production in CD8 T cell lines and clones. We then examine recently degranulated CD8 cells from recall cultures from four middle aged HLA-A2 subjects and show that these functional cells are polyclonal. The clonotype distributions of the CD8(+)CD107(+) repertoires are complex in the same manner as previously reported. The clonotype composition of CD8(+)CD107(+) repertoires is also very similar to CD8 only repertoires, and to CD8(+)HLA-A2-M1(58-66) pentamer positive repertoires. We postulate that multiple exposures during childhood to this conserved influenza A epitope has generated a complex functional repertoire in HLA-A2 individuals.
authors.affiliation: Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Zhou
authors.forename: Maryam B
authors.initials: MB
authors.lastname: Yassai
authors.forename: Jeyarani
authors.initials: J
authors.lastname: Regunathan
authors.forename: Jodie
authors.initials: J
authors.lastname: Box
authors.forename: Dmitry
authors.initials: D
authors.lastname: Bosenko
authors.forename: Yashu
authors.initials: Y
authors.lastname: Vashishath
authors.forename: Wendy
authors.initials: W
authors.lastname: Demos
authors.forename: Fong
authors.initials: F
authors.lastname: Lee
authors.forename: Jack
authors.initials: J
authors.lastname: Gorski
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D052118:Lysosomal-Associated Membrane Protein 1; C488936:M1 protein, Influenza A virus; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014763:Viral Matrix Proteins; D007371:Interferon-gamma