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.

Abstract

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 HTLV-1 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.

• Authors: S Yashiki, T Fujiyoshi, N Arima, M Osame, M Yoshinaga, Y Nagata, M Tara, K Nomura, A Utsunomiya, S Hanada, K Tajima, S Sonoda
• Journal: AIDS research and human retroviruses (AIDS Res Hum Retroviruses) Vol. 17 Issue 11 Pg. 1047-61 (Jul 20 2001) ISSN: 0889-2229 [Print] United States
• PMID: 11485622 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes
• Gene Products, tax
• HLA-A Antigens
• HLA-A*26 antigen
• HLA-B Antigens
• Viral Envelope Proteins

Topics

• Adult
• Age Factors
• Aged
• Alleles
• Amino Acid Motifs
• Amino Acid Sequence
• Carrier State (immunology, virology)
• Cell Line
• Epitopes
• Female
• Gene Products, tax (immunology)
• Genes, MHC Class I (genetics)
• Genetic Predisposition to Disease
• HLA-A Antigens (genetics)
• HLA-B Antigens (genetics)
• Humans
• In Vitro Techniques
• Japan
• Leukemia-Lymphoma, Adult T-Cell (genetics)
• Male
• Middle Aged
• Molecular Sequence Data
• T-Lymphocytes, Cytotoxic (immunology)
• Viral Envelope Proteins (immunology)