10.3389/fimmu.2018.02539.s002
Meriem Attaf
Meriem
Attaf
Amna Malik
Amna
Malik
Mai C. Severinsen
Mai C.
Severinsen
Julia Roider
Julia
Roider
Paul Ogongo
Paul
Ogongo
Søren Buus
Søren
Buus
Thumbi Ndung'u
Thumbi
Ndung'u
Alasdair Leslie
Alasdair
Leslie
Henrik N. Kløverpris
Henrik
N. Kløverpris
Philippa C. Matthews
Philippa
C. Matthews
Andrew K. Sewell
Andrew
K. Sewell
Philip Goulder
Philip
Goulder
Image_2_Major TCR Repertoire Perturbation by Immunodominant HLA-B*44:03-Restricted CMV-Specific T Cells.tiff
Frontiers
2018
T cell
T cell receptor
cytomegalovirus
HLA-B*44:03
repertoire
sequencing
2018-11-14 04:15:53
Figure
https://frontiersin.figshare.com/articles/figure/Image_2_Major_TCR_Repertoire_Perturbation_by_Immunodominant_HLA-B_44_03-Restricted_CMV-Specific_T_Cells_tiff/7336964
<p>Lack of disease during chronic human cytomegalovirus (CMV) infection depends on the maintenance of a high-frequency CMV-specific T cell response. The composition of the T cell receptor (TCR) repertoire underlying this response remains poorly characterised, especially within African populations in which CMV is endemic from infancy. Here we focus on the immunodominant CD8+ T cell response to the immediate-early 2 (IE-2)-derived epitope NEGVKAAW (NW8) restricted by HLA-B<sup>*</sup>44:03, a highly prevalent response in African populations, which in some subjects represents >10% of the circulating CD8+ T cells. Using pMHC multimer staining and sorting of NW8-specific T cells, the TCR repertoire raised against NW8 was characterised here using high-throughput sequencing in 20 HLA-B<sup>*</sup>44:03 subjects. We found that the CD8+ T cell repertoire raised in response to NW8 was highly skewed and featured preferential use of a restricted set of V and J gene segments. Furthermore, as often seen in immunity against ancient viruses like CMV and Epstein-Barr virus (EBV), the response was strongly dominated by identical TCR sequences shared by multiple individuals, or “public” TCRs. Finally, we describe a pair “superdominant” TCR clonotypes, which were germline or nearly germline-encoded and produced at remarkably high frequencies in certain individuals, with a single CMV-specific clonotype representing up to 17% of all CD8+ T cells. Given the magnitude of the NW8 response, we propose that this major skewing of CMV-specific immunity leads to massive perturbations in the overall TCR repertoire in HLA-B<sup>*</sup>44:03 individuals.</p>