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Shaikh M Atif, Sophie L Gibbings, Ronald G Gill, Kenneth M Murphy, Todd Grazia, Raul M Torres, Peter M Henson, Gwendalyn J Randolph, Claudia Jakubzick, Coordinated immune activation by distinct mononuclear phagocytes subtypes against the mismatch of minor antigens, The Journal of Immunology, Volume 196, Issue 1_Supplement, May 2016, Page 116.14, https://doi.org/10.4049/jimmunol.196.Supp.116.14
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Abstract
Recently, we identified that Batf3-dependent DCs were solely responsible for the rejection of minor antigen-mismatched grafts, and demonstrated in Batf3−/− female mice, lacking Batf3-dependent DCs, the complete acceptance of minor antigen-mismatched male cells, which are normally rejected in WT female mice. Intriguingly, this rejection occurs in the absence of PAMPs, leading to considerable uncertainty of how endogenous APC subtypes become activated and licensed to induce an adaptive immune response against male cells in female mice. Investigating this gap in knowledge is the main goal of this study. Rejection of minor antigen-mismatched grafts involves all branches of the immune system: adaptive immunity (T cells), humoral immunity (B cells) and innate immunity (DCs and antigen-presenting monocytes). Although we showed that depletion of one cell type dampens or omits the inflammatory outcome of minor antigen-mismatched graft rejection, here we show how lymphoid and myeloid cell subtypes act sequentially and in concert for the induction of minor antigen-mismatched graft rejection without the presence of PAMPs. In conclusion, we believe that understanding the mechanisms of action against minor antigen-mismatched graft rejection will also apply more broadly to other diseases such as autoimmunity and cancer, in which an immune response is elicited against self-associated minor antigens.
