A small allelic variant in donor class I MHC is sufficient to induce alloantibodies following transfusion of standard or pathogen-reduced platelets in mice.

Background And Objectives: Alloimmunization targeting major histocompatibility (MHC) antigens is common following platelet transfusion. Pathogen reduction of platelets can block alloimmunization to MHC in mice and induce partial antigen-specific tolerance to subsequent transfusions. This study utilized small allelic variants to evaluate the relative contributions of class I and class II MHC to the alloresponse against untreated or pathogen-reduced platelets.

Materials And Methods: C57BL/6 (B6) K and B6 IA mice with small variants in the class I K and class II IA alleles, respectively, were used as platelet donors for wild-type B6 recipients. Both untreated and pathogen-reduced platelet-rich plasma (PRP) transfusions were evaluated for immunogenicity by measuring antibody responses and ex vivo cytokine production.

Results: Both the K and IA alleles induced antibody responses, though the response to K was greater. Pathogen reduction blocked the antibody responses to IA , but not to K . Both the K and IA alleles primed ex vivo cytokine responses that were blocked with pathogen reduction, though responses to IA were broader and larger (K responses: IFN-γ, TNFα, and MIP-1β; IA responses: IFN-γ, TNFα, IL-1β, IL-10, IL-13, and GM-CSF). Pathogen-reduced K PRP did not appear to induce any tolerance to subsequent untreated K PRP transfusions.

Conclusion: Minor allelic variants in both the class I and class II MHC are capable of inducing an alloresponse to transfusion. The K PRP induced alloantibodies even with pathogen reduction and did not show signs of inducing the partial tolerance to subsequent transfusions observed with a larger MHC mismatch.