Epitopes described in "HLA-DM constrains epitope selection in the human CD4 T cell response to vaccinia virus by favoring the presentation of peptides with longer HLA-DM-mediated half-lives."

Reference
Article Authors:Liusong Yin; J Mauricio Calvo-Calle; Omar Dominguez-Amorocho; Lawrence J Stern
Article Title:HLA-DM constrains epitope selection in the human CD4 T cell response to vaccinia virus by favoring the presentation of peptides with longer HLA-DM-mediated half-lives.
Reference Detail
Reference ID:1026928
Abstract:HLA-DM (DM) is a nonclassical MHC class II (MHC II) protein that acts as a peptide editor to mediate the exchange of peptides loaded onto MHC II during Ag presentation. Although the ability of DM to promote peptide exchange in vitro and in vivo is well established, the role of DM in epitope selection is still unclear, especially in human response to infectious disease. In this study, we addressed this question in the context of the human CD4 T cell response to vaccinia virus. We measured the IC(50), intrinsic dissociation t(1/2), and DM-mediated dissociation t(1/2) for a large set of peptides derived from the major core protein A10L and other known vaccinia epitopes bound to HLA-DR1 and compared these properties to the presence and magnitude of peptide-specific CD4(+) T cell responses. We found that MHC II-peptide complex kinetic stability in the presence of DM distinguishes T cell epitopes from nonrecognized peptides in A10L peptides and also in a set of predicted tight binders from the entire vaccinia genome. Taken together, these analyses demonstrate that DM-mediated dissociation t(1/2) is a strong and independent factor governing peptide immunogenicity by favoring the presentation of peptides with greater kinetic stability in the presence of DM.
Date:2012
Reference Type:Literature
PubMed ID:22966084
Journal:J Immunol
Journal Volume:189
Article Pages:3983-94
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;HLA-D Antigens;HLA-DM antigens;Peptide Fragments;Viral Proteins
Article MeSH List:Amino Acid Sequence; Antigen Presentation(immunology); Binding, Competitive(immunology); CD4-Positive T-Lymphocytes(immunology; metabolism; virology); Cell Line; Epitopes, T-Lymphocyte(immunology; metabolism); HLA-D Antigens(chemistry; physiology); Half-Life; Humans; Molecular Sequence Data; Peptide Fragments(chemistry; metabolism); Protein Binding(immunology); Vaccinia virus(immunology); Viral Proteins(chemistry; metabolism)
Curation Last Updated:2014-04-01 22:22:42