A common minimal motif for the ligands of HLA-B*27 class I molecules

CD8(+) T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA) class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties...

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Detalles Bibliográficos
Autores: Barriga, Alejandro, Lorente, Elena, Johnstone, Carolina, Mir-Gerrero, Carmen, Val, Margarita del, Lopez, Daniel
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6886
Acceso en línea:http://hdl.handle.net/20.500.12105/6886
Access Level:acceso abierto
Palabra clave:Amino Acid Motifs
Animals
Antigen Presentation
Antigens, Viral, Tumor
Cell Line
HLA-B27 Antigen
Humans
Ligands
Mice
Protein Binding
Protein Stability
Respiratory Syncytial Virus, Human
Viral Proteins
Descripción
Sumario:CD8(+) T cells identify and kill infected cells through the specific recognition of short viral antigens bound to human major histocompatibility complex (HLA) class I molecules. The colossal number of polymorphisms in HLA molecules makes it essential to characterize the antigen-presenting properties common to large HLA families or supertypes. In this context, the HLA-B*27 family comprising at least 100 different alleles, some of them widely distributed in the human population, is involved in the cellular immune response against pathogens and also associated to autoimmune spondyloarthritis being thus a relevant target of study. To this end, HLA binding assays performed using nine HLA-B*2705-restricted ligands endogenously processed and presented in virus-infected cells revealed a common minimal peptide motif for efficient binding to the HLA-B*27 family. The motif was independently confirmed using four unrelated peptides. This experimental approach, which could be easily transferred to other HLA class I families and supertypes, has implications for the validation of new bioinformatics tools in the functional clustering of HLA molecules, for the identification of antiviral cytotoxic T lymphocyte responses, and for future vaccine development.