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Antigen‐specific dose‐dependent system for the study of an inheritable and reversible phenotype in mouse CD4 + T cells
Author(s) -
Firpo Eduardo J.,
Kong Raymond K.,
Zhou Qinghong,
Rudensky Alexander Y.,
Roberts James M.,
Franza B. Robert
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01540.x
Subject(s) - biology , phenotype , microbiology and biotechnology , major histocompatibility complex , context (archaeology) , antigen , cell division , antigen presentation , intracellular , t cell , cell , immune system , immunology , genetics , gene , paleontology
Summary The transgenic T‐cell receptor in mouse TEa CD4 + lymphocytes recognizes an endogenous peptide, Eα52‐68, presented in the context of the major histocompatibility complex class II molecule I‐A b . In response to an optimal peptide concentration TEa cells enter the cell cycle and proliferate. However, a single exposure to high doses of the specific peptide diminished cell expansion upon subsequent restimulation. This hyporesponsive, or anergic, phenotype can still be detected after multiple restimulations indicating that the hyporesponsiveness persists despite cell division and it was inherited by daughter cells. Furthermore, we demonstrated that this hypoproliferative response is associated with high p27 Kip1 and cyclin E protein levels, and reduced intracellular interleukin‐2 (IL‐2) expression. Addition of exogenous IL‐2 was required to reset p27 Kip1 levels in the progeny derived from hyporesponsive TEa cells. Thus, we have established antigen dose‐dependent induction of a reversible, inheritable (i.e. epigenetic) phenotype and we have identified at least three components of the network of interactions: p27 Kip1 cyclin E, and IL‐2 expression.