In chronic infection, HIV gag-specific CD4+ T cell receptor diversity is higher than CD8+ T cell receptor diversity and is associated with less HIV quasispecies diversity.
In chronic infection, HIV gag-specific CD4+ T cell receptor diversity is higher than CD8+ T cell receptor diversity and is associated with less HIV quasispecies diversity.
复制标题
在慢性感染中，HIV gag特异性CD4 T细胞受体多样性高于CD8 T细胞受体多样性，并且与较少的HIV准种多样性相关。
DOI：
10.1128/jvi.02380-20
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发表时间：
2021
影响因子：
5.4
通讯作者：
Kalams,SpyrosA
中科院分区：
文献类型：
--
作者：
Pilkinton,MarkA;McDonnell,WyattJ;Barnett,Louise;Chopra,Abha;Gangula,Rama;White,KatieD;Leary,Shay;Currenti,Jennifer;Gaudieri,Silvana;Mallal,SimonA;Kalams,SpyrosA
Cellular immune responses to Gag correlate with improved HIV control. The full extent of cellular immune responses comprises both the number of epitopes recognized by CD4+and CD8+T cells and the diversity of the T cell receptor (TCR) repertoire directed against each epitope. The optimal diversity of the responsive TCR repertoire is unclear. Therefore, we evaluated the TCR diversity of CD4+and CD8+T cells responding to HIV-1 Gag to determine if TCR diversity correlates with clinical or virologic metrics. Previous studies of TCR repertoires have been limited primarily to CD8+T cell responses directed against a small number of well-characterized T cell epitopes restricted by specific human leukocyte antigens. We stimulated peripheral blood mononuclear cells from 21 chronic HIV-infected individuals overnight with a pool of HIV-1 Gag peptides, followed by sorting of activated CD4+and CD8+T cells and TCR deep sequencing. We found Gag-reactive CD8+T cells to be more oligoclonal, with a few dominant TCRs comprising the bulk of the repertoire, compared with the highly diverse TCR repertoires of Gag-reactive CD4+T cells. HIV sequencing of the same donors revealed that high CD4+T cell TCR diversity was strongly associated with lower HIV Gag genetic diversity. We conclude that the TCR repertoire of Gag-reactive CD4+T helper cells displays substantial diversity without a clearly dominant circulating TCR clonotype, in contrast to a hierarchy of dominant TCR clonotypes in the Gag-reactive CD8+T cells, and may serve to limit HIV diversity during chronic infection.IMPORTANCEHuman T cells recognize portions of viral proteins bound to host molecules (human leukocyte antigens) on the surface of infected cells. T cells recognize these foreign proteins through their T cell receptors (TCRs), which are formed by the assortment of several available V, D, and J genes to create millions of combinations of unique TCRs. We measured the diversity of T cells responding to the HIV Gag protein. We found that the CD8+T cell response is primarily made up of a few dominant unique TCRs, whereas the CD4+T cell subset has a much more diverse repertoire of TCRs. We also found there was less change in the virus sequences in subjects with more diverse TCR repertoires. HIV has a high mutation rate, which allows it to evade the immune response. Our findings describe the characteristics of a virus-specific T cell response that may allow it to limit viral evolution.
