Disparate immune responses to Mi-HAg occur in vitro and in vivo (141.1)

Abstract

Abstract Historically, insights into the mechanism of alloresponses to minor histocompatibility antigen (Mi-HAg) disparities have focused on T cell activity and used in vitro assays. It was believed that prior in vivo immunization was required for T cell responses to Mi-HAg to occur in vitro. Here, we investigated the generation of adaptive immune responses to Mi-HiAg using an in vivo model. We found that AKR (H-2k) mice rejected skin grafts from MHC-matched, Mi-HAg-disparate B10.BR (H-2k) mice and generated significantly high levels of anti-donor Ab, suggesting that skin graft rejection was associated with the initiation of strong adaptive humoral responses. As B cell activation requires signaling from activated T cells, in vitro and in vivo MLR assays were performed to examine the immune response to Mi-HAg. AKR cells exhibited no reactivity to Mi-HAg disparate stimulators in in vitro MLR assays. In contrast, T cells from AKR mice exhibited strong reactivity in in vivo MLR assays to Mi-HAg in B10.BR mice. The reason for this disparity in response to Mi-HAg in vitro vs. in vivo MLR is not clear. The in vitro culture environment may lack some factors that were present in vivo and that are critical for generation of T cell immune responses to Mi-HAg. T cells were indeed activated in response to Mi-HAg, as CD44highCD62L-/low effector/memory T cells were generated. 2:02 p.m.