2D affinity measurements of primary and secondary polyclonal CD4+ effector T cells in lymphocytic choriomenengitis infection (P6121)

Abstract

Abstract T cells have been shown to undergo affinity/avidity maturation through selective expansion of higher affinity/avidity (tetramer positive) cells, resulting in the narrowing of the antigen specific repertoire over the course of primary and secondary immune responses. Using a highly sensitive two dimensional micropipette adhesion frequency assay (2D) to measure polyclonal CD4+ T cell affinities, we determined if affinity maturation occurred between primary and secondary peak effectors in lymphocytic choriomenengitis virus (LCMV) infection, and if measured affinities correlated with functional avidity. The 2D assay detected 4-5 fold more antigen specific high and low affinity cells than tetramer in both primary and secondary infection, but both 2D and tetramer indicated a 2-3 fold decrease in the frequency of LCMV specific CD4+ cells in the homologous viral rechallenge response. The range of affinities of the antigen specific repertoire was more restricted during secondary infection contracting to a narrower sixteen fold from the wider hundred fold range of the primary response. By functional avidity, secondary effectors were more sensitive to antigen despite a 3 fold decrease in their measured average affinity. Therefore, in this homologous viral rechallenge model, affinity maturation did not occur between primary and secondary effectors, and affinity did not correlate with functional avidity.