Modulation of CD8+ T cell response to antigen by the levels of self MHC class I

The Journal of Immunology : Official Journal of the American Association of Immunologists
F R SantoriS Vukmanović

Abstract

The response of H-Y-specific TCR-transgenic CD8(+) T cells to Ag is characterized by poor proliferation, cytolytic activity, and IFN-gamma secretion. IFN-gamma secretion, but not cytotoxic function, can be rescued by the B7.1 molecule, suggesting that costimulation can selectively enhance some, but not all, effector CD8(+) T cell responses. Although the H-Y epitope binds H-2D(b) relatively less well than some other epitopes, it can induce potent CTL responses in nontransgenic mice, suggesting that the observed poor responsiveness of transgenic CD8(+) T cells cannot be ascribed to the epitope itself. Previously reported reactivity of this TCR to H-2A(b) is also not the cause of the poor responsiveness of the H-Y-specific CD8(+) T cells, as H-Y-specific CD8(+) T cells obtained from genetic backgrounds lacking H-2A(b) also responded poorly. Rather, reducing the levels of H-2(b) class I molecules by breeding the mice to (C57BL/6 x B10.D2)F(1) or TAP1(+/-) backgrounds partially restored cytotoxic activity and enhanced proliferative responses. These findings demonstrate that the self MHC class I gene dosage may regulate the extent of CD8(+) T cell responsiveness to Ag.

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Citations

Oct 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zu T ShenLawrence J Stern
Nov 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·F R SantoriS Vukmanovic
Mar 5, 2003·Immunological Reviews·Irena StefanovaRonald N Germain
Oct 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ali Jabbari, John T Harty
Apr 18, 2018·Immunological Reviews·Jae-Ho Cho, Jonathan Sprent
Jan 12, 2019·Human Vaccines & Immunotherapeutics·Neda Mousavi-NiriJamshid Hadjati
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sophie Tourdot, Keith G Gould

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