A Subtle Role for Cd2 in T Cell Antigen Recognition

A fter the demonstration almost 20 years ago that anti-bodies to CD2 are potent inhibitors of T cell function, this cell surface glycoprotein became one of the most intensively studied of all T cell antigens (1–3). The subsequent identification of LFA-3 (CD58) as a ligand for human CD2 led to the demonstration in cell culture experiments that the CD2–CD58 interaction dramatically enhanced T cell anti-gen recognition (1–3). Given this background, it was puzzling that no abnormality in T cell function was observed in the initial experiments on CD2-deficient mice (4, 5). A subsequent study did detect some alteration in T cell development and peripheral T cell responses, but the precise nature of the abnormality was unclear (6). Now work by Bach-mann and colleagues, described in this issue (7), has clarified matters by demonstrating that T cells from CD2-deficient mice have a quantitative defect in antigen recognition: they require a higher concentration of antigen to produce the same response as wild-type T cells. CD2 has an extracellular portion with two Ig-like domains , a single membrane-spanning region, and a positively charged, proline-rich cytoplasmic domain, which is highly conserved between species (2, 8). It is expressed on T cells and NK cells in all mammalian species studied to date, but is also found on B cells in the mouse and splenic macrophages in the rat and sheep (9). A more significant species difference is that in the mouse and rat, which do not express CD58, the major CD2 ligand is CD48 (8). Conversely, human CD2 binds very weakly to CD48. CD2 and its ligands, CD48 and CD58, are members of a family of structurally related cell surface molecules termed the CD2 family, which includes signaling lymphocytic activation molecule (SLAM), CD84, Ly-9, and 2B4 (8, 10). The observation that these molecules bind members of the same family suggests that the CD2 family evolved from a common ancestral gene that encoded a homophilic adhesion molecule. Further support for this notion has come from the recent demonstration that 2B4 binds CD48 (11), and that SLAM self-associates (12). It has also been reported that human CD2 binds the structurally unrelated molecule CD59, but this is controversial (8). The strategy used by Bachmann et al. to study CD2 function was to cross CD2-deficient mice with transgenic mice expressing a TCR specific for the lymphocytic chorio-meningitis virus (LCMV)–derived peptide, p33. In the absence of CD2, peripheral T cells …