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1.
J Immunol ; 202(10): 2849-2855, 2019 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-30936292

RESUMEN

Cytotoxic CD8+ T lymphocytes (CTLs) recognize peptides displayed by HLA class I molecules on cell surfaces, monitoring pathological conditions such as cancer. Difficulty in predicting HLA class I ligands is attributed to the complexity of the Ag processing pathway across the cytosol and the endoplasmic reticulum. By means of HLA ligandome analysis using mass spectrometry, we collected natural HLA class I ligands on a large scale and analyzed the source-protein sequences flanking the ligands. This comprehensive analysis revealed that the frequency of proline at amino acid positions 1-3 upstream of the ligands was selectively decreased. The depleted proline signature was the strongest among all the upstream and downstream profiles. Experiments using live cells demonstrated that the presence of proline at upstream positions 1-3 attenuated CTL responses against a model epitope. Other experiments, in which N-terminal-flanking Ag precursors were confined in the endoplasmic reticulum, demonstrated an inability to remove upstream prolines regardless of their positions, suggesting a need for synergistic action across cellular compartments for making the proline signature. Our results highlight, to our knowledge, a unique role and position of proline for inhibiting downstream epitope presentation, which provides a rule for defining natural peptide-HLA class I repertoire formation and CTL responses.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Inmunidad Celular , Péptidos/inmunología , Linfocitos T CD8-positivos/citología , Línea Celular , Antígenos de Histocompatibilidad Clase I/química , Humanos , Péptidos/química , Prolina/química , Prolina/inmunología
2.
Hemoglobin ; 45(2): 129-132, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33874827

RESUMEN

The proband was a male in his seventies who came to our facility because of shortness of breath. He was not anemic but presented dissociation between oxygen saturation (SpO2) and partial pressure of oxygen (PaO2) by blood gas analysis, and also demonstrated hemoglobinopathy after measurement of Hb A1c using high performance liquid chromatography (HPLC). Twenty-three percent of unknown hemoglobin (Hb) bands were detected. After sequencing the ß-globin gene, we noted a missense mutation at codon 74 (GGC>CGC) (Gly→Arg) of the ß-globin chain and he was diagnosed with Hb Aalborg (HBB: c.223G>C). One of the proband's siblings was diagnosed to have a low SpO2 level and also diagnosed to carry Hb Aalborg; she was also mildly anemic. This is the first known familial case of Hb Aalborg in Japan. In addition to Hb Aalborg, our case had underlying chronic obstructive pulmonary disease (COPD). Herein we present this case as a rare addition to the hematological literature.


Asunto(s)
Hemoglobinas Anormales , Enfermedad Pulmonar Obstructiva Crónica , Femenino , Hemoglobinas Anormales/genética , Humanos , Japón , Masculino , Saturación de Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/genética , Globinas beta/genética
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