HTLV-I env protein acts as a major antigen in patients with HTLV-I-associated arthropathy.
Our objective was to investigate the pathological mechanisms of HTLV-I (human T-cell leukemia virus type I)-associated chronic arthritis (HAAP) with respect to T-cell response to HTLV-I viral proteins. We examined T-cell clonality and the antigen recognized by T cells from the inflamed synovium of patients with HAAP by using histology, a single-strand conformation polymorphism (SSCP) analysis and T cell receptor (TCR) sequencing. The SSCP analysis showed oligoclonal expansion of T cells in the synovium, suggesting an antigen-mediated stimulation. In contrast, there was less clonal expansion in peripheral blood lymphocytes (PBL). The expression of HTLV-1 env and tax mRNA was detected in the affected synovium as well as in PBL. A number of T-cell clones in the synovium recognized HTLV-I env and tax proteins. Twenty-seven (24.9%) of 109 examined T-cell clones in the joints were HTLV-I env reactive, and 7 clones (6.4%) were HTLV-I tax reactive. Junctional sequence analysis of synovial T cells showed a lack of highly conserved amino acid motifs in the complementarity-determining region 3 (CDR3) of HTLV-I env and tax reactive T cells, suggesting that these cells recognized multiple T-cell epitopes on HTLV-I antigen. These findings suggest that HTLV-I env protein acts as a major antigen and may play a role in the development of arthropathy in patients with HAAP.
Rheumatology Program, Department of Bioregulation, Institute of Medical Science, St Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, 216-8512, Kawasaki, Japan. t3kato@marianna-u.ac.jp
Tomohiro
T
Kato
Hiroshi
H
Asahara
Manae Suzuki
MS
Kurokawa
Koushi
K
Fujisawa
Tomoko
T
Hasunuma
Hajime
H
Inoue
Masanao
M
Tsuda
Shigeru
S
Takahashi
Satoru
S
Motokawa
Takayuki
T
Sumida
Kusuki
K
Nishioka
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis; D000956:Antigens, Viral / Q000276:immunology*; D001170:Arthritis, Infectious / Q000276:immunology* / Q000821:virology; D001483:Base Sequence; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000235:genetics; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D016356:Gene Products, tax / Q000235:genetics / Q000276:immunology; D015490:HTLV-I Infections / Q000150:complications / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D000956:Antigens, Viral; D022801:Complementarity Determining Regions; D015686:Gene Products, env; D016356:Gene Products, tax; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell