Anti-Tcrb Monoclonal antibody, clone I68-608 [PE/Cy5®]

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 alpha or beta clonotypes per subject) comprised thousands of unique TCRa and TCRb sequences and dozens of distinct complementary determining region (CDR) 3 alpha and CDR3 beta motifs. However, diversity is effectively restricted by preferential V-J combinations, CDR3 lengths, and CDR3a/ CDR3b 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(+) TCRb 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.

Defects in T cell receptor (TCR) repertoire are proposed to predispose to autoimmunity. Here we show, by analyzing >2 x 108 TCRB sequences of circulating naive, central memory, regulatory and stem cell-like memory CD4(+) T cell subsets from patients with type 1 diabetes and healthy donors, that patients have shorter TCRB complementarity-determining region 3s (CDR3), in all cell subsets, introduced by increased deletions/reduced insertions during VDJ rearrangement. High frequency of short CDR3s is also observed in unproductive TCRB sequences, which are not subjected to thymic culling, suggesting that the shorter CDR3s arise independently of positive/negative selection. Moreover, TCRB CDR3 clonotypes expressed by autoantigen-specific CD4(+) T cells are shorter compared with anti-viral T cells, and with those from healthy donors. Thus, early events in thymic T cell development and repertoire generation are abnormal in type 1 diabetes, which suggest that short CDR3s increase the potential for self-recognition, conferring heightened risk of autoimmune disease.