T-Cell Epitopes in Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Protein Elicit a Specific T-Cell Immune Response in Patients Who Recover from SARS

Abstract

The immunogenicity of HLA-A2-restricted T-cell epitopes in the S protein of the Severe acute respiratory syndrome coronavirus (SARS-CoV) and of human coronavirus strain 229e (HCoV-229e) was analyzed for the elicitation of a T-cell immune response in donors who had fully recovered from SARS-CoV infection. We employed online database analysis to compare the differences in the amino acid sequences of the homologous T epitopes of HCoV-229e and SARS-CoV. The identified T-cell epitope peptides were synthesized, and their binding affinities for HLA-A2 were validated and compared in the T2 cell system. The immunogenicity of all these peptides was assessed by using T cells obtained from donors who had fully recovered from SARS-CoV infection and from healthy donors with no history of SARS-CoV infection. HLA-A2 typing by indirect immunofluorescent antibody staining showed that 51.6% of SARS-CoV-infected patients were HLA-A2 positive. Online database analysis and the T2 cell binding test disclosed that the number of HLA-A2-restricted immunogenic epitopes of the S protein of SARS-CoV was decreased or even lost in comparison with the homologous sequences of the S protein of HCoV-229e. Among the peptides used in the study, the affinity of peptides from HCoV-229e (H77 and H881) and peptides from SARS-CoV (S978 and S1203) for binding to HLA-A2 was higher than that of other sequences. The gamma interferon (IFN-␥) release Elispot assay revealed that only SARS-CoV-specific peptides S1203 and S978 induced a high frequency of IFN-␥-secreting T-cell response in HLA-A2؉ donors who had fully recovered from SARS-CoV infection; such a T-cell epitope-specific response was not observed in HLA-A2؉ healthy donors or in HLA-A2 ؊ donors who had been infected with SARS-CoV after full recovery. Thus, T-cell epitopes S1203 and S978 are immunogenic and elicit an overt specific T-cell response in HLA-A2 ؉ SARS-CoV-infected patients.

Screening and Identification of Severe Acute Respiratory Syndrome-Associated Coronavirus-Specific CTL Epitopes

“…The SARS-CoV infects epithelial cells in the respiratory tract causing interstitial pneumonia and elicits strong immune responses (58). Memory or surviving effector CTLs against S978 and S1203 epitopes have been reported to be detectable from SARS-recovered donors 2 mo after the onset of disease (31). In this study, CTLs still existed in the donors 7-8 mo after SARS-CoV infection and were presumably from the memory CTL pool.…”

“…A 193-aa small fragment within the S1 domain (S318 -510) was identified as a minimal receptor domain and contained multiple conformationdependent epitopes that induce highly potent neutralizing Abs (29,30). Recently, three S protein-derived CTL epitopes SSp-1 (S1167), S987, and S1203 were identified by two groups (31,32). These epitopes, however, were all screened from nonamer libraries.…”

Elicitation of Immunity in Mice After Immunization with the S2 Subunit of the Severe Acute Respiratory Syndrome Coronavirus

“…Moreover, the HLA-A2-restricted T-cell epitopes in the S2 domain of SARS-CoV could elicit T-cell immune response in donors who had fully recovered from SARS-CoV infection (Wang et al, 2004). This means that although the S2 subunit makes few contributions to inducing virus-neutralizing antibodies, we should not absolutely give up using it as a full or partial candidate antigen before obtaining protection results.…”

Response of Memory CD8+ T Cells to Severe Acute Respiratory Syndrome (SARS) Coronavirus in Recovered SARS Patients and Healthy Individuals

“…SARS-associated lymphopenia has also been well documented (8 -10), but the underlying mechanism remains unknown. Some previous studies demonstrated the absolute counts of lymphocytes and lymphocyte subsets to be a useful indicator in the development of effective methods of diagnosis and treatment of SARS (11,12), and three HLA-A*0201-restricted CD8 ϩ T cell epitopes, SSp-1, S978, and S1202, were recently identified from SARS-CoV spike protein (13)(14)(15).…”

“…Although memory T cell responses to epitopes S1202 and S978 were detected in an IFN-␥ ELISPOT assay in PBMCs from HLA-A*0201 ϩ recovered SARS patients up to 3 mo postinfection (14,15), how long this immunity will last requires further monitoring. Surprisingly, in the generation of effector CTLs from healthy donors without any contact history with SARS-CoV following in vitro repeated challenge of PBMCs with heat-inactivated SARSCoV-pulsed dendritic cells in culture medium supplemented with IL-7, IL-10, and IL-2, inactivated SARS-CoV provoked recall-like T cell responses in certain healthy donors, which hints that there might exist memory T cell populations cross-reactive to SARSCoV.…”