IngentaConnect Human CD4 T lymphocytes recognize a highly conserved epitope of h...

Authors: Kitze¹; Usuku²; Yamano³; Yashiki³; Nakamura⁴; Fujiyoshi³; Izumo¹; Osame²; Sonoda³

Source: Clinical & Experimental Immunology, Volume 111, Number 2, February 1998 , pp. 278-285(8)

Abstract:

HTLV-1 causes two distinct human diseases, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T cell leukaemia/lymphoma (ATL). Persistently infected individuals carry a risk of < 1% of developing either disease. These basic epidemiological data imply that virus-host interactions, especially immunogenetic factors, influence the outcome of infection. Several studies showed that the HLA class II DR1 DQ5 haplotype is over-represented in HAM/TSP, but rare in ATL. Therefore, we selected four patients with HAM/TSP and one seronegative control who all carried the HLA DR1 DQ5 haplotype. We analysed the CD4⁺ T lymphocyte response against eight synthetic peptides of HTLV-1 envelope (env) glycoprotein gp21, a crucial target antigen in HAM/TSP. The first of two immunodominant epitopes corresponded to a domain of the HTLV-1 envelope protein which had previously been shown to be essential for HTLV-1 envelope function. The second immunodominant epitope overlapped a highly conserved sequence of the retroviral transmembrane envelope protein. DR1 (DRB1*0101)-restricted T lymphocytes were activated by the conserved peptide sequence in nanomolar concentrations. In contrast, this conserved sequence can also induce non-specific, cAMP-mediated immunosuppressive effects on T cells when added in micromolar concentrations to culture media, as shown by Haraguchi S, Good RA, James-Yarish M, Cianciolo GJ, Day NK, Proc Natl Acad Sci USA 1995; 92:5568-71. Hence, HTLV-1 env gp21 might exert either stimulating immunological or immunosuppressive effects in HTLV-1-infected individuals, depending on the level of its expression and the presence of HLA DRB1*0101.

Keywords: HTLV-1; T lymphocytes; epitope; HLA

Document Type: Original article

DOI: 10.1046/j.1365-2249.1998.00497.x

Affiliations: 1: Centre for Chronic Viral Diseases, 2: Third Department of Internal Medicine, 3: Department of Virology, Faculty of Medicine, Kagoshima University, Kagoshima, 4: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan

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Human CD4+ T lymphocytes recognize a highly conserved epitope of human T lymphotropic virus type 1 (HTLV-1) env gp21 restricted by HLA DRB1*0101

Human CD4⁺ T lymphocytes recognize a highly conserved epitope of human T lymphotropic virus type 1 (HTLV-1) env gp21 restricted by HLA DRB1*0101