Profiling the repertoire of TCRB usage in induced and natural Treg cells (62.5)

Abstract

Abstract In our recent research, we have found that a subset of all possible T cell receptor beta (TCRB) rearrangements is produced more frequently than expected in unrelated individuals. This subset appears to be defined by rearrangements that are near to germline, with relatively few non-templated nucleotides inserted at the V-D and D-J junctions within complementarity determining region 3. The degree of overlap between TCRB repertoire between individuals does not appear to be dramatically HLA context-dependent. Other groups have described several subsets of regulatory CD4 T cells (Treg), including both thymus-derived natural Tregs (nTregs) and peripherally induced Tregs (iTregs). While both subtypes express the FOXP3 transcription factor that defines them as regulatory T cells, it has been asserted that the expression of a second transcription factor (Helios) can differentiate nTregs (Helios+) from induced Tregs (Helios-). We hypothesize that the nTreg population is likely to be enriched for near-germline TCRB rearrangments, as recurrently produced TCRB that predispose to the nTreg fate are likely to be shared between individuals. We will compare and contrast the TCRB repertoire in three cellular populations within several individuals: CD4+ FoxP3- Helios-, CD4+ FoxP3+ Helios-, and CD4+ FoxP3+ Helios+.