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.

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 with HAM/TSP than 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 with HAM/TSP showed similar Vbeta 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.

• Authors: 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
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 196 Issue 12 Pg. 1761-72 (Dec 15 2007) ISSN: 0022-1899 [Print] United States
• PMID: 18190256 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-A Antigens
• HLA-DRB1 Chains
• HLA-DRB1*01:01 antigen
• HTLV-I Antigens
• Histocompatibility Antigens Class II
• Immunodominant Epitopes
• RNA, Messenger
• Receptors, Antigen, T-Cell

Topics

• Alleles
• Amino Acid Sequence
• CD4-Positive T-Lymphocytes (immunology)
• Female
• Genes, pX (genetics, immunology)
• Genetic Predisposition to Disease
• HLA-A Antigens (genetics, immunology)
• HLA-DRB1 Chains
• HTLV-I Antigens (immunology)
• Histocompatibility Antigens Class II (genetics, immunology)
• Human T-lymphotropic virus 1 (immunology, isolation & purification)
• Humans
• Immunodominant Epitopes (immunology)
• Leukocytes, Mononuclear (immunology, virology)
• Male
• Middle Aged
• Molecular Sequence Data
• Paraparesis, Tropical Spastic (genetics, immunology, virology)
• Phenotype
• RNA, Messenger (biosynthesis, genetics)
• Receptors, Antigen, T-Cell (immunology)
• Viral Load