Genetic Control of T Lymphocyte Responses by in Vitro Sensitization with Macrophage-Bound Antigens

Abstract

The genetic factors involved in the guinea pig response to the copolymer of l-glutamic acid and l-lysine (GL), responsiveness which is linked to the I-region of the strain 2 major histocompatibility complex, have been further analyzed by in vitro priming of nonimmune T lymphocytes with GL-pulsed syngeneic or semi-syngeneic macrophages. Responder strain 2 T cells could be specifically sensitized by culture for a week with GL-pulsed strain 2 macrophages and produced an increased DNA synthetic response upon restimulation with GL in the presence of fresh strain 2 macrophages. In contrast, nonresponder strain 13 T cells failed to become sensitized to GL-pulsed strain 13 macrophages, but could be specifically primed by culture with ovalbumin (OVA)-pulsed strain 13 macrophages. In addition, (2 × 13)F₁ T cells primed by culture with GL-pulsed strain 2 or (2 × 13)F₁ macrophages could be restimulated with GL only in the presence of strain 2, but not of strain 13, macrophages. F₁ T cells failed to demonstrate sensitization with GL-pulsed nonresponder strain 13 macrophages, but showed OVA-specific priming with OVA-pulsed strain 13 macrophages. These results indicate that genetic control of the response to GL by in vitro sensitization with GL-pulsed macrophages is similar to that previously observed by immunization of guinea pigs with soluble GL and support the proposal that unresponsiveness to GL represents a defect in cellular recognition.