RESUMO
The purpose of the present study is to perform a global screening for new immunogenic HLA class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes of potential utility as candidates of influenza A-virus diagnostics and vaccines. We used predictions of antigen processing and presentation, the latter encompassing 12 different HLA class I supertypes with >99% population coverage, and searched for conserved epitopes from available influenza A viral protein sequences. Peptides corresponding to 167 predicted peptide-HLA-I interactions were synthesized, tested for peptide-HLA-I interactions in a biochemical assay and for influenza-specific, HLA-I-restricted CTL responses in an IFN-gamma ELISPOT assay. Eighty-nine peptides could be confirmed as HLA-I binders, and 13 could be confirmed as CTL targets. The 13 epitopes, are highly conserved among human influenza A pathogens, and all of these epitopes are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential.
Assuntos
Epitopos de Linfócito T/imunologia , Antígenos HLA-A/imunologia , Antígenos HLA-B/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Animais , Aves , Feminino , Testes Genéticos , Genoma Viral , Humanos , Virus da Influenza A Subtipo H5N1/genética , Vírus da Influenza A/genética , Influenza Aviária/virologia , Influenza Humana/sangue , Influenza Humana/virologia , Masculino , Proteínas de Membrana Transportadoras/imunologia , Proteínas de Membrana Transportadoras/metabolismo , Pessoa de Meia-Idade , Complexo de Endopeptidases do Proteassoma/metabolismo , Linfócitos T Citotóxicos/virologiaRESUMO
A 47-yr-old female with acute pancreatitis received four units of fresh frozen plasma because of subtle signs of disseminated intravascular coagulation (DIC). Seven days later, she developed severe thrombocytopenia. Serological studies demonstrated antibodies against HPA-1a together with pan-reactive antibodies against platelet glycoproteins (GPIIb-IIIa, GPIb-IX and GPIa-IIa), which was consistent with the diagnosis of PTP. The patient was treated with platelet transfusions, corticosteroids and intravenous immunoglobulin (IVIG) without permanent beneficial effect. After treatment with plasma exchange the platelet count increased to normal values.
