Does the signal for the activation of T cells originate from the antigen-presenting cell or the effector T-helper?

The present view is that the antigen-presenting cell (APC) processes and presents simultaneously on its surface several different antigens that are displayed randomly (with respect to their being Self or Nonself) as peptide–MHC complexes. The naive T-cell interacting with its ligand on the APC is activated by “co-stimulation,” the first step on the pathway to effectors. This view ignores the requirement for associative recognition of antigen (ARA) in mediating both the Self–Nonself discrimination and the regulation of effector class. The introduction of ARA as a requirement for these two decision functions highlights a critical role for the effector T-helper (eTh) and necessitates rethinking the contribution of the APC.