In vitro cytotoxic T cell responses to cell-free minor histocompatibility antigens. Requirement for antigen-presenting cells

Although it has been documented that antigen-presenting cells (APC) are required for the response to minor histocompatibility antigens (MIHA) on membrane fragments, there is no evidence to indicate whether or not these APC actually process MIHA. In this manuscript we identify these APC as Ia+, Thy 1.2-, Ly6.1-, Ly7.2-, Ly5- adherent cells. They cannot be replaced by soluble adherent cell products, including interleukin-1 (IL-1), or by interleukin-2, and are required for at least the first 4 hr of a cytotoxic T lymphocyte (CTL) response. After this period, the response can continue in the absence of either adherent cells or the MIHA-bearing membrane fragments, indicating that the APC function is required for the initiation of a response. If APC are inactivated by heat treatment prior to exposure to the MIHA-bearing fragments, they are unable to contribute to the triggering of a CTL response. However, if these cells are inactivated by heat after exposure to MIHA, they are fully able to contribute to the induction of a CTL response. We interpret these results as an indication that metabolic activity is required for antigen uptake--but, once this has occurred, an inactivated APC is still able to present MIHA. This suggests the involvement of a requisite early antigen-processing event by APC that is distinct from the putative association of MIHA with H-2.