The functional CD8 T cell memory recall repertoire responding to the influenza A M158–66 epitope is polyclonal and shows a complex clonotype distribution

Autor: Wendy Demos, D.V. Bosenko, Yashu Vashishath, Maryam Yassai, Vivian Zhou, Fong Lee, Jeyarani Regunathan, Jodie Box, Jack Gorski
Rok vydání: 2013
Předmět:
Zdroj: Human Immunology. 74:809-817
ISSN: 0198-8859
DOI: 10.1016/j.humimm.2012.12.016
Popis: 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.
Databáze: OpenAIRE