The structure and ligand interactions of CD2: implications for T-cell function
Davis SJ, van der Merwe PA. (1996), Immunol Today. 17, 177-87
Considerable progress has recently been made in understanding the structure and ligand interactions of the T-cell antigen CD2, to the extent that CD2 is now a useful paradigm for considering the structural basis of cell-cell recognition. Here, Simon Davis and Anton van der Merwe review the new data and consider their implications for T-cell function in the context of CD2-knockout experiments.
Key figure: Dimensions of CD2 and other T-cell surface molecules: implications for T-cell triggering
(a) Scale models are shown of some of the key molecules present at the cell surface during the interaction of T cells with APCs, based on crystallography or electron microscopy data44,74,96. (b) On resting T cells, the TCR/CD3 complex and other molecules involved in antigen recognition are expected to be randomly distributed among much larger molecules such as CD45. (c) It is proposed that binding of CD2 to its ligand(s) leads to close membrane approximation within multiple contact zones between the T cell and APC. In addition to optimizing the interaction between the TCR and peptide-MHC (Ref. 74), membrane approximation may exclude CD45 from the contact zone, thereby extending the half-life of any tyrosine-phosphorylated signalling intermediate in the adjacent cytoplasm. This model postulates that TCR triggering requires stable complexes (e.g. complex II), which remain in the contact zone long enough for completion of all the requisite steps in the signal transduction pathway. For clarity, only CD2, CD4/Lck, CD45 and the TCR/CD3 complex have been depicted in (b) and (c). This model of TCR triggering is described in more detail in Box 2. Abbreviations: APC, antigen-presenting cell; GPI, glycosylphosphatidylinositol; IgSF, immunoglobulin superfamily; ITAM, immunoreceptor tyrosine-based activation motif; LFA-1, leukocyte function-associated molecule 1; MHC, major histocompatibility complex; TCR, T-cell receptor.