ISSN Print 2500–1094
ISSN Online 2542–1204
Bulletin of RSMU
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
ORIGINAL RESEARCH
Estimating the number of HIV-specific T-cells in healthy donors using high-throughput sequencing profiles of T-cell receptor repertoires
About authors
Pirogov Russian National Research Medical University, Moscow, Russia
Correspondence should be addressed: Mikhail Shugay
ul. Miklukho-Maklaya, d. 16/10, Moscow, Russia, 117997; moc.liamg@yaguhs.liahkim
About paper
Funding: this work was supported by the Russian Science Foundation (Grant No. 17-15-01495).
All authors' contribution to this work is equal: selection and analysis of literature, research planning, data collection, analysis, and interpretation, drafting of a manuscript, editing.
Received: 2017-10-23
Accepted: 2017-10-28
Published online: 2018-01-14
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Fig. 1. Mean abundance of different HIV-specific T-cell receptors (TCR) in the T-cell repertoires sequenced by Emerson et al. [14] and Britanova et al. [15]. The X-axis represents distribution of an average-sized clonotypic population derived from an HIV-specific T-cell (fraction of all TCR beta chain reads) in the samples from [14] (n = 65) and [15] (n = 601). The Y-axis represents epitopes for which HIV-specific TCR sequences are known (according to VDJdb); data format: HLA allele : epitope sequence
Fig. 2. Abundance of HIV-specific TCR in the sample of individuals with known cytomegalovirus status. Results for CMV-positive (+) and CMV-negative (–) individuals are provided separately for each epitope. Plotted along the X-axis is the common logarithm of an average-sized clonotypic population of an HIV-specific T-cell (fraction of total TCR beta chain reads). Data have been winsorized for graphical clarity: the figure shows samples with values ranging between the 5th and 95th percentiles
Fig. 3. The total frequency of TCR specific to HIV-epitopes represented by donor’s HLA allele sets (data borrowed from Emerson et al.). Plotted along the X-axis is mean percent (for groups of individuals with the studied HLA allele) of the total number of reads for TCR sequences specific to HIV epitopes represented by a specific HLA allele. Standard deviation is provided for each value. The list of alleles was obtained by intersecting datasets from VDJdb and annotations from Emerson et al. study. Allele HLA-B*42 was excluded from the analysis, because it was represented by only one sample. Other alleles were present in more than 35 of 601 donors. Protective alleles and alleles associated with susceptibility to HIV were borrowed from Goulder and Walker’s work [3]
Fig. 4. Changes in the total frequency of HIV-specific TCR in donors of different sex and age. Data from Emerson et al. are distributed into groups based on the CMV status of the participants. The graph also shows results of linear modeling for HIV-specific TCR dependence on age for males and females
