IDENTIFYING TCR BLOCKING HLA SPECIFIC ANTIBODIES AS POTENTIAL THERAPEUTICS IN ACHIEVING TRANSPLANT TOLERANCE

MARYAM HAMIDINIA

Publication

IDENTIFYING TCR BLOCKING HLA SPECIFIC ANTIBODIES AS POTENTIAL THERAPEUTICS IN ACHIEVING TRANSPLANT TOLERANCE

MARYAM HAMIDINIA

Abstract

Over the last decades, organ transplantation as a curative therapy for organ failure has made rapid progress. However, the adaptive immune system, such as T cells and antibodies targeting human leukocyte antigens (HLA), are the leading cause for graft rejection. The presence of anti-donor HLA Abs is considered a risk factor that disqualifies a particular donor-recipient pair. However, protective blocking function of allo-antibodies has been suggested, and allo-antibodies have been found in some long-term graft survivors. Therefore, the role of allo-antibodies in transplantation remains unclear. Here, A*1101-specific monoclonal IgG1 antibodies were generated from a non-immune human library, and the effect of antibodies was investigated on A*1101-restricted syngeneic primary T cells and a T cell line expressing a known TCR specific for A*1101. We identified an A*1101-specific monoclonal IgG1 antibody with the capacity to block TCR recognition, to decrease T cell activation and CD3 recruitment to the immune synapse. Furthermore, this antibody reduces translocation of NFAT1 transcription factor and the phosphorylation of pERK protein.