Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Journal of Negative Results in Biomedicine

Esper G Kallas¹  Mario A Ostrowski³  Douglas F Nixon²  Aluisio C Segurado¹  Aaron M Hasenkrug²  Fabio E Leal¹  R Brad Jones³ 

[1] Department of Infectious Diseases, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil;Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA;Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON, Canada

关键词: HTLV-1-associated myelopathy/tropical spastic paraparesis;    T-cells;    Human endogenous retrovirus;    HTLV-I;   

Others  :  814655
DOI  :  10.1186/1477-5751-12-3

 received in 2012-04-20, accepted in 2012-12-23,  发布年份 2013

【 摘 要 】

Background

An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial.

Results

Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets.

Conclusions

Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

【 授权许可】

   
2013 Jones et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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