tetano
Editor, Senior Moderator
Cell Rep. 2017 Apr 18;19(3):569-583. doi: 10.1016/j.celrep.2017.03.072.
[h=1]Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens.[/h] Chen G[SUP]1[/SUP], Yang X[SUP]2[/SUP], Ko A[SUP]1[/SUP], Sun X[SUP]1[/SUP], Gao M[SUP]2[/SUP], Zhang Y[SUP]3[/SUP], Shi A[SUP]1[/SUP], Mariuzza RA[SUP]2[/SUP], Weng NP[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP] TCR repertoires for two dominant viral epitopes: pp65[SUB]495-503[/SUB] (NLV) of cytomegalovirus and M1[SUB]58-66[/SUB] (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[SUP]+[/SUP] 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.
Copyright ? 2017. Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] CD8 T cells; TCR repertoire; TCR-pMHC structure; human; αβ TCRs for CMV-NLV; αβ TCRs for IAV-GIL
PMID: 28423320 DOI: 10.1016/j.celrep.2017.03.072
[h=1]Sequence and Structural Analyses Reveal Distinct and Highly Diverse Human CD8+ TCR Repertoires to Immunodominant Viral Antigens.[/h] Chen G[SUP]1[/SUP], Yang X[SUP]2[/SUP], Ko A[SUP]1[/SUP], Sun X[SUP]1[/SUP], Gao M[SUP]2[/SUP], Zhang Y[SUP]3[/SUP], Shi A[SUP]1[/SUP], Mariuzza RA[SUP]2[/SUP], Weng NP[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+[/SUP] TCR repertoires for two dominant viral epitopes: pp65[SUB]495-503[/SUB] (NLV) of cytomegalovirus and M1[SUB]58-66[/SUB] (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[SUP]+[/SUP] 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.
Copyright ? 2017. Published by Elsevier Inc.
[h=4]KEYWORDS:[/h] CD8 T cells; TCR repertoire; TCR-pMHC structure; human; αβ TCRs for CMV-NLV; αβ TCRs for IAV-GIL
PMID: 28423320 DOI: 10.1016/j.celrep.2017.03.072