Sharing of class I MHC molecules between donor and host promotes the infiltration of allografts by mHAg-reactive CD8⁺ T cells

Indirect recognition of minor histocompatibility antigens (mHAg) and/or MHC-encoded allopeptides is an important barrier to long-term allograft acceptance following solid organ transplantation. Efficient priming of CD8 ⁺ T cells can occur after allotransplantation as a consequence of cross-presentation of donor-derived proteins by the graft recipient's APC. Consistent with this, draining lymph node clonal expansion of OVA-reactive OT-ICD8⁺ T cells following placement of OVA-transgenic skin grafts did not depend on graft expression of K^b. However, OT-I T cells did accumulate in OVA-transgenic skin grafts most efficiently only when both the donor and host expressed K^b. OT-I infiltration of (B6-OVA × BALB/c)F₁ grafts in B6 recipients was not suppressed by graft expression of H-2^d. Furthermore, B6 animals transplanted with both B6-OVA and BALB/c-OVA skin had more OT-I T cells infiltrating their B6-OVA MHC-matched graft. Therefore, class I MHC matching between donor and host may not always favor an avoidance of alloreactivity within the graft tissue.