Public TCR use by herpes simplex Virus-2–specific human CD8 CTLs

L Dong, P Li, T Oenema, CL McClurkan… - The Journal of …, 2010 - journals.aai.org
L Dong, P Li, T Oenema, CL McClurkan, DM Koelle
The Journal of Immunology, 2010journals.aai.org
Recombination of germline TCR α and β genes generates polypeptide receptors for MHC
peptide. Ag exposure during long-term herpes simplex infections may shape the T cell
repertoire over time. We investigated the CD8 T cell response to HSV-2 in chronically
infected individuals by sequencing the hypervariable regions encoding TCR α and β
polypeptides from T cell clones recognizing virion protein 22 aa 49–57, an immunodominant
epitope. The most commonly detected TCRBV gene segment, found in four of five subjects …
Abstract
Recombination of germline TCR α and β genes generates polypeptide receptors for MHC peptide. Ag exposure during long-term herpes simplex infections may shape the T cell repertoire over time. We investigated the CD8 T cell response to HSV-2 in chronically infected individuals by sequencing the hypervariable regions encoding TCR α and β polypeptides from T cell clones recognizing virion protein 22 aa 49–57, an immunodominant epitope. The most commonly detected TCRBV gene segment, found in four of five subjects and in 12 of 50 independently derived T cell clones, was TCRBV12-4. Nineteen to seventy-two percent of tetramer-binding cells in PBMCs were stained ex vivo with a TCRBV12 mAb. Three α-chain and three β-chain public TCR sequences were shared between individuals. Public heterodimers were also detected. Promiscuous pairing of a specific TCRVA1-1 sequence with several different TCRB polypeptides was observed, implying a dominant structural role for the TCRA chain for these clonotypes. Functional avidity for cytotoxicity and IFN-γ release was relatively invariant, except for one subject with both high avidity and unique TCR sequences and lower HSV-2 shedding. These data indicate that the CD8 response to a dominant α-herpesvirus epitope converges on preferred TCR sequences with relatively constant functional avidity.
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