HLA-A*26, HLA-B*4002, HLA-B*4006, and HLA-B*4801 alleles predispose to adult T cell leukemia:: The limited recognition of HTLV type 1 tax peptide anchor motifs and epitopes to generate anti-HTLV type 1 tax CD8+ cytotoxic T lymphocytes

被引:63
作者
Yashiki, S
Fujiyoshi, T
Arima, N
Osame, M
Yoshinaga, M
Nagata, Y
Tara, M
Nomura, K
Utsunomiya, A
Hanada, S
Tajima, K
Sonoda, S
机构
[1] Kagoshima Univ, Fac Med, Dept Virol, Kagoshima 8908520, Japan
[2] Kagoshima Univ, Fac Med, Dept Internal Med 1, Kagoshima 8908520, Japan
[3] Kagoshima Univ, Fac Med, Dept Internal Med 3, Kagoshima 8908520, Japan
[4] Kagoshima Univ, Fac Med, Dept Obstet & Gynecol, Kagoshima 8908520, Japan
[5] Kagoshima ATL Study Grp, Kagoshima, Japan
[6] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent Med, Nagoya, Aichi 4640021, Japan
关键词
D O I
10.1089/088922201300343735
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Genetic risk for adult T cell leukemia (ATL) has been implicated by ethnic and familial segregation of ATL patients from HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To clarify the genetic risk for ATL, we characterized HLA class I alleles of ATL patients and analyzed the anchor motifs of HTLVI peptides binding to HLA class I molecules, using 291 lines of anti-HTLV-1 CD8(+) cytotoxic T lymphocytes (CTLs) generated in vitro with a total of 165 synthetic peptides for HTLV-1 Tax and Env proteins. Allele frequencies of HLA-A*26, B*4002, B*4006, and B*4801 were significantly higher in ATL patients than in HAM/TSP patients and asymptomatic HTLV-1 carriers in southern Japan. CD8(+) CTL analysis revealed the HTLV-1 Tax peptide sequence to completely lack anchor motifs of peptides binding to HLA-A*26,B*4002, and B*4006 molecules but to possess one anchor for HLA-B*4801, while the HTLV-1 Env peptide sequence had many anchor motifs for HLA-A*26, B*4002, B*4006, and B*4801 molecules. Most ATL patients featured heterozygous HLA class I alleles composed of HLA-A*26, B*4002, B*4006, and B*4801, with a lower number of HTLV-1 Tax peptide anchor motifs and epitopes generating anti-HTLV-1 Tax CD8(+) CTLs than individuals possessing other HLA alleles. The relationship between Tax epitope and ATL incidence was verified by the significantly decreased number of HTLV-1 Tax epitopes in ATL patients compared with asymptomatic HTLV-1 carriers (p < 0.01) as well as late onset ATL patients (p < 0.001). These results indicate that HLA-A*26, B*4002, B*4006, and B*4801 alleles predispose to ATL because of the limited recognition of HTLV-1 Tax peptide anchor motifs and epitopes capable of generating anti-HTLV-1 Tax CD8(+) CTLs.
引用
收藏
页码:1047 / 1061
页数:15
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