[PDF][PDF] Sequence and structural analyses reveal distinct and highly diverse human CD8+ TCR repertoires to immunodominant viral antigens

G Chen, X Yang, A Ko, X Sun, M Gao, Y Zhang, A Shi… - Cell reports, 2017 - cell.com
G Chen, X Yang, A Ko, X Sun, M Gao, Y Zhang, A Shi, RA Mariuzza, N Weng
Cell reports, 2017cell.com
A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections.
However, information about TCR repertoires to defined viral antigens is limited. We
performed a comprehensive analysis of CD8+ TCR repertoires for two dominant viral
epitopes: pp65 495–503 (NLV) of cytomegalovirus and M1 58–66 (GIL) of influenza A virus.
The highly individualized repertoires (87–5,533 α or β clonotypes per subject) comprised
thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary …
Summary
A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8+ TCR repertoires for two dominant viral epitopes: pp65495–503 (NLV) of cytomegalovirus and M158–66 (GIL) of influenza A virus. The highly individualized repertoires (87–5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3α/CDR3β pairings. Structures of two GIL-specific TCRs bound to GIL–HLA-A2 provided a potential explanation for the lower diversity of GIL-specific versus NLV-specific repertoires. These anti-viral TCRs occupied up to 3.4% of the CD8+ TCRβ repertoire, ensuring broad T cell responses to single epitopes. Our portrait of two anti-viral TCR repertoires may inform the development of predictors of immune protection.
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