Co-Receptors in the Positive and Negative Regulation of T-Cell Immunity

  • Helga Schneider
  • Christopher E. Rudd


Engagement of the antigen-receptor complex (TcRζ/CD3) on T cells is insufficient for the development of an optimal response against foreign antigen. Instead, T cells require at least two signals for optimal T-cell expansion (Bretscher 1999). Peptides presented to antigen-specific T cells in the context of major histocompatibility complex (MHC) molecules deliver signal 1, whereas a co-stimulatory signal through a distinct T-cell surface molecule triggers signal 2. Signaling through signal 1, in the absence of co-stimulation, leads to aborted activation and often a state of anergy or clonal unresponsiveness (Schwartz 1990). T-cell activation can occur in the absence of signal 2 under conditions where the TcR signal is very strong (i.e., high avidity peptide). With the advancement of the field, it is now apparent that there exists an array of different co-receptors on T cells (Fig. 1). These include CD28, inducible T-cell co-stimulator (ICOS) and cytotoxic T-cell antigen (CTLA-4), programmed death-1 (PD-1), B and T lymphocyte attenuator (BTLA) and T-cell immunoglobulin and mucin-domain-containing molecule- 3 (Tim-3). As will be outlined in this review, each of these receptors provides unique and overlapping signals that modulate different aspects of T-cell immunity.


Immunological Synapse Herpes Virus Entry Mediator PI3K Binding 


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Copyright information

© Springer 2008

Authors and Affiliations

  • Helga Schneider
    • 1
  • Christopher E. Rudd
    • 1
  1. 1.Cell Signalling Section, Division of Immunology, Department of PathologyUniversity of CambridgeCambridgeUK

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