Identification of HLA-A*01- and HLA-A*02-restricted CD8+ T-cell epitopes shared among group B enteroviruses

Abstract

Acute enteroviral infections ranging from meningitis, pancreatitis to myocarditis are common and normally well controlled by the host immune system comprising virus-specific CD8 + cytotoxic T lymphocytes (CTL). However, in some patients enteroviruses and especially coxsackieviruses of group B are capable of inducing severe chronic forms of diseases such as chronic myocarditis. Currently, it is not known whether divergences in the CTL-related immune response may contribute to the different outcome and course of enterovirus myocarditis. A pre-requisite for the study of CTL reactions in patients with acute and chronic myocarditis is the identification of CTL epitopes. In order to define dominant enterovirus CTL epitopes, we have screened, by using gamma interferon (IFN-c) ELISPOT, 62 HLA-A*01-and 59 HLA-A*02-positive healthy blood donors for pre-existing CTL reactions against 12 HLA-A*01 and 20 HLA-A*02 predicted CTL epitopes derived from coxsackieviruses of group B. Positive CTL reactions were verified by FACS analysis in a combined major histocompatibility complex-tetramer IFN-c staining. A total of 14.8 % of all donors reacted against one of the three identified epitopes MLDGHLIAFDY, YGDDVIASY or GIIYIIYKL. The HLA-A*02-restricted epitope ILMNDQEVGV was recognized by 25 % of all tested blood donors. For this peptide, we could demonstrate specific granzyme B secretion, a strong cytolytic potential and endogenous processing. All four epitopes were homologous in 36-92 % of group B enteroviruses, providing a strong basis for monitoring the divergence of T-cellbased immune responses in enterovirus-induced acute and chronic diseases.

Differential Interferon Responses Enhance Viral Epitope Generation by Myocardial Immunoproteasomes in Murine Enterovirus Myocarditis

“…16,46 These data suggest that epitopes from the P3D region may be more effective, which is in accordance with recent findings in human beings. 47 In conclusion, the present study substantiates the impact of type I IFN in the prevention of severe acute and consecutively chronic myocarditis in mice. The primary identification of CVB3 epitopes enabled novel findings with regard to the activity and function of myocardial IP in acute myocarditis.…”

Elicitation of T-cell responses by structural and non-structural proteins of coxsackievirus B4

“…In the case of CV-B4, epitopes in the structural and 2C proteins have previously been mapped using CD4 + T-cell lines (Marttila et al, 2001(Marttila et al, , 2002, whilst the HLA class I-restricted CD8 + epitopes have been mapped in the 3C and 3D proteins of CV-B3 (Weinzierl et al, 2008). The latter study identified four CD8…”

Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection

“…It is well-established that only a fraction of CTL-epi- topes predicted by HLA binding algorithms are in fact recognized by virus specific CD8+ T cells [21]. Herein, we used a peptide binding assay based on UV-induced ligand exchange to rapidly assess which peptides of the HAV polyprotein form true HLA ligands.…”