Unconventional peptide presentation by major histocompatibility complex (MHC) class i allele HLA-A∗02:01: Breaking confinement

• Autores: Remesh, Soumya G.; Andreatta, Massimo; Ying, Ge; Kaever, Thomas; Nielsen, Morten; McMurtrey, Curtis; Hildebrand, William; Peters, Bjoern; Zajonc, Dirk M.
• Año de publicación: 2017
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Mhc; Toxoplasma Gondii; Mass Spec
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Peptide antigen presentation by major histocompatibility complex (MHC) class I proteins initiates CD8+ T cell-mediated immunity against pathogens and cancers.MHCI molecules typically bind peptides with 9 amino acids in length with both ends tucked inside the major A and F binding pockets. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zigzag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLAA∗ 02:01. These peptides were extended at the C terminus (PΩ) and contained charged amino acids not more than 3 residues after the anchor amino acid at PΩ, which enabled them to open the F pocket and expose their C-terminal extension into the solvent. Here, we show that the mechanism of F pocket opening is dictated by the charge of the first charged amino acid found within the extension. Although positively charged amino acids result in the Tyr-84 swing, amino acids that are negatively charged induce a not previously described Lys-146 lift. Furthermore, we demonstrate that the peptides with alternative binding modes have properties that fit very poorly to the conventional MHC class I pathway and suggest they are presented via alternative means, potentially including cross-presentation via the MHC class II pathway.
Fil: Remesh, Soumya G.. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Andreatta, Massimo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Ying, Ge. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Kaever, Thomas. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina. Technical University of Denmark; Dinamarca
Fil: McMurtrey, Curtis. Oklahoma State University; Estados Unidos. Pure MHC LLC; Estados Unidos
Fil: Hildebrand, William. Oklahoma State University; Estados Unidos. Pure MHC LLC; Estados Unidos
Fil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Zajonc, Dirk M.. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of Ghent; Bélgica