RESUMEN
Following the 2009 H1N1 influenza pandemic, an increased risk of narcolepsy type 1 was observed. Homology between an H1N1 hemagglutinin and two hypocretin sequences has been reported. T cell reactivity to these peptides was assessed in 81 narcolepsy type 1 patients and 19 HLA-DQ6-matched healthy controls. HLA-DQ6-restricted H1N1 hemagglutinin-specific T cell responses were detected in 28.4% of patients and 15.8% of controls. Despite structural homology between HLA-DQ6-hypocretin and -H1N1 peptide complexes, T cell cross-reactivity was not detected. These results indicate that it is unlikely that cross-reactivity between H1N1 hemagglutinin and hypocretin peptides presented by HLA-DQ6 is involved in the development of narcolepsy.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Antígenos HLA-DQ/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Narcolepsia/inmunología , Orexinas/inmunología , Subgrupos de Linfocitos T/inmunología , Adolescente , Adulto , Proteínas del Líquido Cefalorraquídeo/análisis , Niño , Cristalografía por Rayos X , Femenino , Antígenos HLA-DQ/química , Cadenas alfa de HLA-DQ/análisis , Cadenas beta de HLA-DQ/análisis , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Humanos , Subtipo H1N1 del Virus de la Influenza A , Masculino , Persona de Mediana Edad , Modelos Moleculares , Imitación Molecular , Narcolepsia/etiología , Orexinas/líquido cefalorraquídeo , Orexinas/química , Pandemias , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Conformación Proteica , Adulto JovenRESUMEN
BACKGROUND: It is now generally accepted that coeliac disease (CD) is caused by inflammatory T cell responses to gluten peptides bound to HLA-DQ2 or -DQ8 molecules. There is overwhelming evidence that CD patients can mount T cell responses to peptides found in both alpha-gliadin and gamma-gliadin molecules. Assays that would detect the presence or absence of such peptides in food would thus be accurate indicators of safety for consumption by CD patients. AIMS: The development of a sensitive method to detect T cell stimulatory epitopes of alpha-gliadin and gamma-gliadin molecules in food products. METHODS: Monoclonal antibodies (mAb) were raised against peptides encoding the T cell stimulatory epitopes of alpha-gliadin (amino acids (aa) 59-71) and aa gamma-gliadin (aa 142-153 and aa 147-159). These mAb competition assays were developed that quantitatively detect T cell stimulatory epitopes present on both intact proteins and peptides of sizes recognisable by CD4(+) T cells. RESULTS: With the mAb based competition assays, T cell epitopes were detected in pepsin/trypsin digests of wheat proteins and ethanol extracts of various food products, with detection levels lower than those reached with gluten specific T cells. Moreover, the presence of T cell stimulatory epitopes was also detected in preparations of barley, rye, and triticale, other cereals known to be toxic for CD patients. CONCLUSIONS: A new antibody based method has been developed, detecting the presence of T cell stimulatory gluten peptides. This can be used to further ensure the safety of food consumed by CD patients.