MHC CONTROL OF LYMPHOCYTE-MACROPHAGE-T INTERACTIONS

Identity at the major histocompatibility complex (MHC) of primed T cells and macrophages was essential for the development of a T cell proliferative response to Purified Protein Derivative of tuberculin (PPD) in the presence of macrophage-associated antigen and potential allogeneic effects were eliminated by the use of one-way fetal liver chimeras as a T cell source. By contrast, such MHC restriction could not be shown for the T cell-macrophage interaction when antigen was present in soluble form. It was found that the proliferative response of primed (responder × nonresponder) F1 T cells to the Ir-gene controlled antigen, TNP-18 [Glu-Tyr-Lys (TNP) (Glu-Tyr-Ala)5], could only be restored by responder macrophages with bound antigen, while both responder and nonresponder macrophages reconstituted the response to soluble TNP-18. Supernatants from cultured responder or nonresponder macrophages could at least partially replace viable macrophages in the latter case. These results argue for two distinct antigen presentation mechanisms, depending on the physical state of the antigen rather than its chemical nature: one involves recognition of antigen in association with MHC-coded determinants and shows H-2 restriction, while the other, mediated by soluble factors and antigen, does not. © 1979 Springer-Verlag New York Inc.