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Increased sensitivity to antigen in high avidity CD8 + T cells results from augmented membrane proximal T‐cell receptor signal transduction
Author(s) -
Sharma Sharad K.,
AlexanderMiller Martha A.
Publication year - 2011
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2011.03440.x
Subject(s) - avidity , t cell receptor , cytotoxic t cell , ctl* , biology , antigen , cd8 , microbiology and biotechnology , t cell , cd3 , signal transduction , immunology , immune system , biochemistry , in vitro
Summary The functional avidity of a cytotoxic T lymphocyte (CTL) is known to be a critical determinant of the efficacy with which it clears pathogens. High avidity cells, which are by definition highly sensitive to peptide antigen, are superior for elimination of viruses and tumours. Our studies have established the ability of T cells to undergo avidity modulation as a result of antigen encounter. High and low avidity cells established in this manner exhibit significant differences in the amount of peptide required to elicit effector function. However, how signalling is regulated in these cells as it relates to the control of peptide sensitivity remains to be defined. To address this question, we compared T‐cell receptor (TCR) signal transduction events in high and low avidity CTL generated from OT‐I rag2− TCR transgenic mice. Our data suggest that divergent signalling is initiated at the TCR‐associated CD3ζ, with low avidity CTL requiring higher amounts of pMHC to achieve threshold levels of phosphorylated CD3ζ compared with high avidity CTL. Further, this difference is transduced further downstream to mitogen‐activated protein kinase and Ca 2+ signalling pathways. These results suggest that regulated control of the initiation of TCR signalling in high versus low avidity cells determines the amount of peptide required for T‐cell activation.