Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Angew Chem Int Ed Engl ; 53(49): 13390-4, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25348595

ABSTRACT

Bioorthogonal cleavable linkers are attractive building blocks for compounds that can be manipulated to study biological and cellular processes. Sodium dithionite sensitive azobenzene-containing (Abc) peptides were applied for the temporary stabilization of recombinant MHC complexes, which can then be employed to generate libraries of MHC tetramers after exchange with a novel epitope. This technology represents an important tool for high-throughput studies of disease-specific T cell responses.


Subject(s)
Azo Compounds/chemistry , HLA-A Antigens/chemistry , Peptides/chemistry , Amino Acid Sequence , Azo Compounds/immunology , Dithionite/chemistry , Epitopes/chemistry , Epitopes/immunology , HLA-A Antigens/immunology , Humans , Ligands , Models, Molecular , Peptides/immunology , Recombinant Proteins/chemistry , Recombinant Proteins/immunology
2.
J Virol ; 88(18): 10613-23, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24990997

ABSTRACT

UNLABELLED: Cytotoxic T lymphocytes recognizing conserved peptide epitopes are crucial for protection against influenza A virus (IAV) infection. The CD8 T cell response against the M158-66 (GILGFVFTL) matrix protein epitope is immunodominant when restricted by HLA-A*02, a major histocompatibility complex (MHC) molecule expressed by approximately half of the human population. Here we report that the GILGFVFTL peptide is restricted by multiple HLA-C*08 alleles as well. We observed that M158-66 was able to elicit cytotoxic T lymphocyte (CTL) responses in both HLA-A*02- and HLA-C*08-positive individuals and that GILGFVFTL-specific CTLs in individuals expressing both restriction elements were distinct and not cross-reactive. The crystal structure of GILGFVFTL-HLA-C*08:01 was solved at 1.84 Å, and comparison with the known GILGFVFTL-HLA-A*02:01 structure revealed that the antigen bound both complexes in near-identical conformations, accommodated by binding pockets shaped from shared as well as unique residues. This discovery of degenerate peptide presentation by both HLA-A and HLA-C allelic variants eliciting unique CTL responses to IAV infection contributes fundamental knowledge with important implications for vaccine development strategies. IMPORTANCE: The presentation of influenza A virus peptides to elicit immunity is thought to be narrowly restricted, with a single peptide presented by a specific HLA molecule. In this study, we show that the same influenza A virus peptide can be more broadly presented by both HLA-A and HLA-C molecules. This discovery may help to explain the differences in immunity to influenza A virus between individuals and populations and may also aid in the design of vaccines.


Subject(s)
Epitopes, T-Lymphocyte/immunology , HLA-A Antigens/immunology , HLA-C Antigens/immunology , Influenza A virus/immunology , Influenza, Human/immunology , T-Lymphocytes, Cytotoxic/immunology , Viral Matrix Proteins/immunology , Amino Acid Sequence , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/genetics , HLA-A Antigens/chemistry , HLA-A Antigens/genetics , HLA-C Antigens/chemistry , HLA-C Antigens/genetics , Humans , Influenza A virus/genetics , Influenza, Human/genetics , Influenza, Human/virology , Interferon-gamma/immunology , Molecular Sequence Data , Sequence Alignment , T-Lymphocytes, Cytotoxic/virology , Viral Matrix Proteins/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...