Triggering of the alternative pathway of human T cell activation involves members of the T 200 family of glycoproteins

Abstract The present report describes functional characteristics of a monoclonal antibody (mAb), TA/211, which is reactive with a common determinant of the human CD45 molecules. When added to purified testing human T cells, TA/211, which is itself not mitogenic, leads to a strong proliferative response in combination with submitogenic concentrations of anti‐T11 2 plus anti‐T11 3 mAb. Interestingly, while amplifying anti‐CD2‐mediated immune responses, T cell activation induced through triggering of the CD3 molecule is not enhanced by TA/211, indicating that the triggering signal provided through CD45 is restricted to alternative pathway activation. Employing T cell subsets negatively selected for the expression of CD45R molecules defined by the mAb anti‐2H4 or UCHL1, respectively, it is demonstrated that resting T cells expressing the 2H4 molecules proliferate much stronger to TA/211 than the UCHL1 1 T cell subset. Together with the finding that the 2H4 T cell subset can be activated by the concomitant binding of anti‐CD2 antibodies plus anti‐2H4, these data strongly suggest that the high molecular weight species of CD45 expressed by unprimed T cells are themselves involved in T cell activation via the alternative pathway.