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) Kbm1 and B6 IAbm12 mice with small variants in the class I Kb and class II IAb 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 Kbm1 and IAbm12 alleles induced antibody responses, though the response to Kbm1 was greater. Pathogen reduction blocked the antibody responses to IAbm12 , but not to Kbm1 . Both the Kbm1 and IAbm12 alleles primed ex vivo cytokine responses that were blocked with pathogen reduction, though responses to IAbm12 were broader and larger (Kbm1 responses: IFN-γ, TNFα, and MIP-1β; IAbm12 responses: IFN-γ, TNFα, IL-1β, IL-10, IL-13, and GM-CSF). Pathogen-reduced Kbm1 PRP did not appear to induce any tolerance to subsequent untreated Kbm1 PRP transfusions.
CONCLUSION: Minor allelic variants in both the class I and class II MHC are capable of inducing an alloresponse to transfusion. The Kbm1 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.