T cells perform critical roles in orchestrating immunity in health and disease. However, decoding what individual T cells recognize has long been challenging due to the immense diversity of both T cell receptors (TCRs) and potential antigens. Recent advances in high-throughput TCR screening approaches now provide an opportunity to map the antigen specificity landscape of T cells with unprecedented depth. Here, we outline these recent developments in screening methodologies and discuss how these can help advance our fundamental understanding of T cell-based immunity.
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