The affinity of MOG specific CD4 + T cells does not predict cross-recognition to NFM in demyelinating autoimmune disease (BA2P.127)

Abstract

Abstract TCRs can recognize and cross-react to multiple antigens, but little is known of how cross-reactivity might contribute to the etiology of demyelinating autoimmune disease. Here we extend the analysis of monoclonal 2D2 TCR cross-reactivity for MOG38-49 (myelin oligodendrocyte glycoprotein) and NFM18-30 (neurofilament medium protein) to polyclonal T cells. Utilization of the 2D micropipette adhesion frequency assay allows definition of antigen specificity and affinity of individual T cells for peptide:MHC ex vivo. We show that the frequency of CD4+ T cells from the CNS recognizing MOG, NFM, or both fluctuate during the course of MOG35-55 induced experimental autoimmune encephalomyelitis. Higher affinity T cells are maintained as a rare population within the repertoire yet the frequency of higher affinity, MOG specific T cells increase to a greater extent than NFM specific T cells during disease and MOG specific T cells exhibit higher affinities (10-4 to 10-3) than NFM specific T cells (<10-4). Importantly, cross-recognition is not limited to higher or lower affinity clones. We have cloned an encephalitogenic T cell that is high affinity for MOG and low affinity for NFM, which contrasts the 2D2 TCR exhibiting a medium affinity for NFM and a very low MOG affinity. On a population level, TCR recognition of one or more CNS antigens is dynamic within the chronic autoimmune repertoire warranting future research to understand their individual contributions to disease.