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Hirohisa Nose, Ryuji Kubota, Nilufer P. Seth, Peter K. Goon, Yuetsu Tanaka, Shuji Izumo, Koichiro Usuku, Yoshiro Ohara, Kai W. Wucherpfennig, Charles R. M. Bangham, Mitsuhiro Osame, Mineki Saito, Ex Vivo Analysis of Human T Lymphotropic Virus Type 1-Specific CD4+ Cells by Use of a Major Histocompatibility Complex Class II Tetramer Composed of a Neurological Disease-Susceptibility Allele and Its Immunodominant Peptide, The Journal of Infectious Diseases, Volume 196, Issue 12, 15 December 2007, Pages 1761–1772, https://doi.org/10.1086/522966
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Abstract
HLA-DRB1⋆0101 is associated with susceptibility to human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Here, we used a synthetic tetramer of DRB1⋆0101 and its epitope peptide to analyze HTLV-1-specific CD4+ T cells ex vivo. The frequency of tetramer+CD4+ T cells was significantly greater in patients withHAM/TSPthan in healthy HTLV-1 carriers (HCs) at a given proviral load and correlated with HTLV-1 tax messenger RNA expression in HCs but not in patients with HAM/TSP. These cells displayed an early to intermediate effector memory phenotype and were preferentially infected by HTLV-1. T cell receptor gene analyses of 2 unrelated DRB1⋆0101-positive patients withHAM/TSPshowed similar Vβ repertoires and amino acid motifs in complementarity-determining region 3. Our data suggest that efficient clonal expansion of virus-specific CD4+ T cells in patients with HAM/TSP does not simply reflect higher viral burden but rather reflects a rapid turnover caused by preferential infection and/or in vivo stimulation by major histocompatibility complex-peptide complexes.
- alleles
- phenotype
- amino acid motifs
- bone marrow diseases
- complementarity determining regions
- disease susceptibility
- epitopes
- genes
- histocompatibility
- histocompatibility antigens class ii
- human t-lymphotropic virus 1
- tropical spastic paraparesis
- peptides
- human placental lactogen
- t-cell receptor
- rna, messenger
- spinal cord diseases
- t-lymphocytes
- viral load result
- infections
- memory
- viruses
- t-cell leukemia viruses, human
- hla-drb1 gene
- complex
- clonal expansion