ABSTRACT
Understanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we profile the repertoire of human leukocyte antigen class II (HLA-II)-bound peptides presented by HLA-DR diverse monocyte-derived dendritic cells pulsed with SARS-CoV-2 spike (S) protein. We identify 209 unique HLA-II-bound peptide sequences, many forming nested sets, which map to sites throughout S including glycosylated regions. Comparison of the glycosylation profile of the S protein to that of the HLA-II-bound S peptides reveals substantial trimming of glycan residues on the latter, likely induced during antigen processing. Our data also highlight the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region and identify S2-derived peptides with potential for targeting by cross-protective vaccine-elicited responses. Results from this study will aid analysis of CD4+ T cell responses in infected individuals and vaccine recipients and have application in next-generation vaccine design.
Subject(s)
COVID-19/immunology , Dendritic Cells/immunology , Histocompatibility Antigens Class II/immunology , Peptides/immunology , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Sequence , Antigen Presentation , COVID-19/virology , Epitope Mapping , Epitopes, T-Lymphocyte/immunology , Glycosylation , Humans , Protein Binding , Protein Interaction Domains and Motifs , SARS-CoV-2/immunology , T-Lymphocytes/immunologyABSTRACT
Understanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we have profiled the repertoire of human leukocyte antigen class II (HLA-II)-bound peptides presented by HLA-DR diverse monocyte-derived dendritic cells pulsed with SARS-CoV-2 spike (S) protein. We identify 209 unique HLA-II-bound peptide sequences, many forming nested sets, which map to sites throughout S including glycosylated regions. Comparison of the glycosylation profile of the S protein to that of the HLA-II-bound S peptides revealed substantial trimming of glycan residues on the latter, likely introduced during antigen processing. Our data also highlight the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region. Results from this study have application in vaccine design, and will aid analysis of CD4+ T cell responses in infected individuals and vaccine recipients.
ABSTRACT
The purpose of this study was to explore whether and in what ways high-achieving school students motivational orientations influence their perceptions of a fictitious future high-achieving classmate. The final sample consisted of the 396 highest achieving students out of a sample from 1794 seventh and tenth graders from five countries: Australia, Peru, South Korea, Spain, and Vietnam. A series of stepwise regression models were used to test the hypothesis that positive perceptions of a highachieving classmate might be mediated by an approach motivation, but not by an avoidance motivational orientation. The hypothesis was generally confirmed. Learning goal orientation and performance approach motivation predicted positive perceptions of a high-achieving classmates intellectual ability, social qualities and popularity among peers, whereas a performance avoidance orientation was usually uncorrelated. However, sporadic exceptions have been found among the participants from Vietnam, South Korea, and Peru
El propósito de este estudio es explorar si las motivaciones de alto logro influencian las percepciones de los alumnos sobre un futuro compañero de clase ficticio que se caracteriza por tener un alto rendimiento; y si es así de qué modo ocurre. La muestra final consistió en 396 alumnos de alto rendimiento que fueron seleccionados de un total de 1794 alumnos de séptimo y decimo grado de cinco países: Australia, Perú, Corea del sur, España y Vietnam. Se llevaron a cabo una serie de modelos de regresión por pasos sucesivos para probar la hipótesis de que las percepciones positivas sobre un compañero de alto rendimiento podrían estar mediadas por el enfoque motivacional, pero no por la orientación a la evitación del trabajo. La hipótesis fue confirmada en su generalidad. Las metas orientadas al manejo del aprendizaje y las orientadas al alto rendimiento predijeron percepciones positivas de la habilidad intelectual, cualidades sociales y popularidad entre los compañeros del alumno de alto rendimiento, mientras que las metas de evitación del trabajo no obtuvieron correlaciones significativas. Sin embargo, se dieron algunas excepciones esporádicas entre los participantes de Vietnam, Corea del sur y Perú