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Titolo:
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
Autore:
Yashiki, S; Fujiyoshi, T; Arima, N; Osame, M; Yoshinaga, M; Nagata, Y; Tara, M; Nomura, K; Utsunomiya, A; Hanada, S; Tajima, K; Sonoda, S;
Indirizzi:
Kagoshima Univ, Fac Med, Dept Virol, Kagoshima 8908520, Japan Kagoshima Univ Kagoshima Japan 8908520 t Virol, Kagoshima 8908520, Japan Kagoshima Univ, Fac Med, Dept Internal Med 1, Kagoshima 8908520, Japan Kagoshima Univ Kagoshima Japan 8908520 l Med 1, Kagoshima 8908520, Japan Kagoshima Univ, Fac Med, Dept Internal Med 3, Kagoshima 8908520, Japan Kagoshima Univ Kagoshima Japan 8908520 l Med 3, Kagoshima 8908520, Japan Kagoshima Univ, Fac Med, Dept Obstet & Gynecol, Kagoshima 8908520, Japan Kagoshima Univ Kagoshima Japan 8908520 Gynecol, Kagoshima 8908520, Japan Kagoshima ATL Study Grp, Kagoshima, Japan Kagoshima ATL Study Grp Kagoshima Japan ATL Study Grp, Kagoshima, Japan Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent Med, Nagoya, Aichi 4640021, Japan Aichi Canc Ctr Nagoya Aichi Japan 4640021 d, Nagoya, Aichi 4640021, Japan
Titolo Testata:
AIDS RESEARCH AND HUMAN RETROVIRUSES
fascicolo: 11, volume: 17, anno: 2001,
pagine: 1047 - 1061
SICI:
0889-2229(20010720)17:11<1047:HHHAHA>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
I-ASSOCIATED MYELOPATHY; HLA-CLASS-I; HIV-SEROPOSITIVE INDIVIDUALS; TROPICAL SPASTIC PARAPARESIS; NEUROLOGICAL DISEASE; SYNTHETIC PEPTIDES; MELANOMA PATIENTS; CTL EPITOPE; VIRUS; IDENTIFICATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Sonoda, S Kagoshima Univ, Fac Med, Dept Virol, 8-35-1 Sakuragaok, Kagoshima 8908520,Japan Kagoshima Univ 8-35-1 Sakuragaok Kagoshima Japan 8908520 ,Japan
Citazione:
S. Yashiki et al., "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", AIDS RES H, 17(11), 2001, pp. 1047-1061

Abstract

Genetic risk for adult T cell leukemia (ATL) has been implicated by ethnicand 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.

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Documento generato il 07/08/20 alle ore 07:04:10