Relative contribution of major histocompatibility complex antigens to the immunogenicity of corneal allografts

The relative contributions made by the major class I (RT1.A) and class II (RT1.B) antigens of the rat major histocompatibility complex (MHC) to the immunogenicity of corneal and skin allografts were investigated using congenic animals. PVG (RT1c) recipients were given skin or heterotopic cornea grafts from congenic PVG.1A (RT1a) or PVG.R1 (RT1r1) donors, which respectively share the entire RT1 complex or only the RT1.A (major class I MHC antigen) region with fully allogeneic ACI (RT1a) rats. Recipient splenocytes were tested at ten days posttransplant for their ability to lyse ACI, PVG.1A, PVG.R1, and PVG target cells in a secondary CML following 6 days in vitro stimulation with irradiated ACI spleen cells. Effector cells from PVG recipients of both RT1.A and B disparate (PVG.1A donor) and RT1.A disparate (PVG.R1) skin or cornea grafts lysed ACI, PVG.1A, and PVG.R1 (but not PVG) targets at levels significantly above controls given syngeneic grafts. However, the level of cytotoxicity against PVG.R1 as well as ACI and PVG.1A allogeneic targets was always significantly higher following PVG.1A grafts than following PVG.R1 grafts, indicating that the addition of a class II MHC antigen difference markedly augmented the immunogenicity of class I MHC antigen disparate cornea and skin grafts. Taken together with other recent evidence confirming the presence of Langerhans cells in the normal rat (and human) cornea, these results suggest that class II MHC-bearing cells make an important contribution to the immunogenicity of corneal allografts.