Partial deletions of the cytoplasmic domain of CD2 result in a partial defect in signal transduction

CD2 (T11, the T cell erythrocyte receptor or the SRBC receptor), a nonpolymorphic 47- to 55-kDa glycoprotein, appears to play a role in T lymphocyte adhesion, signal transduction, and differentiation. Pairs of anti-CD2 mAb induce T cell proliferation, suggesting that CD2 may be an Ag-independent pathway of T cell activation. We have expressed the human CD2 and a number of cytoplasmic domain deletion mutants of CD2 in an Ag-reactive murine hybridoma. We have previously shown that a cytoplasmic domain deletion mutant, CD2ΔB, in which the carboxyl-terminal 100 amino acids have been deleted, is no longer capable of signaling through CD2. Here we have expressed a second cytoplasmic domain deletion mutant, CD2ΔS, in which the terminal 41 amino acids have been removed, including the region with greatest conservation between the mouse, rat, and human species. CD2ΔS⁺ hybridomas were able to respond to Ag and to LFA-3 plus an anti-CD2 mAb. Although the CD2ΔS⁺ hybridomas responded comparably to the wild-type CD2⁺ hybridomas to certain pairs of anti-CD2 mAb (e.g., MT110 + 9-1 mAb), these CD2ΔS⁺ hybridomas were markedly deficient in their ability to respond to other pairs of stimulatory anti-CD2 mAb (e.g., 9.6 + 9-1 mAb). These data suggest that the cytoplasmic domain may have several functional regions, as partial deletions of the cytoplasmic domain appear to result in partial defects in signal transduction.