Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance

6533b838fe1ef96bd12a52aa

RESEARCH PRODUCT

Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance

Anne Burgevin Anne Burgevin Søren Buus Mirjana Weimershaus Mirjana Weimershaus P Van Endert Hansjörg Schild Mikkel Harndahl Guillaume Stewart-jones Jan Gerstoft Andrew J. Mcmichael Kasper Lamberth Paul Klenerman L Friis Nadja Akkad Stefan Tenzer Iversen Akn.E Y Jones E Wee Chang C-h.Lars Fugger

subject

Models Molecular Proteasome Endopeptidase Complex HIV Antigens Molecular Sequence Data Immunology Antigen presentation HIV Core Protein p24 HIV Infections Immunodominance Major histocompatibility complex gag Gene Products Human Immunodeficiency Virus Epitope Evolution Molecular Major Histocompatibility Complex Leucyl Aminopeptidase 03 medical and health sciences 0302 clinical medicine Antigen Humans Immunology and Allergy Cytotoxic T cell Amino Acid Sequence 030304 developmental biology Antigen Presentation 0303 health sciences HLA-A Antigens biology Immunodominant Epitopes Antigen processing Virology 3. Good health CTL*Mutation HIV-1 biology.protein ATP-Binding Cassette Transporters Protein Binding T-Lymphocytes Cytotoxic 030215 immunology

description

Udgivelsesdato: 2009-May-03 Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group-associated antigen proteins p17 and p24 correlated with epitope abundance, which was strongly influenced by proteasomal digestion profiles, affinity for the transporter protein TAP, and trimming mediated by the endoplasmatic reticulum aminopeptidase ERAAP, and was moderately influenced by HLA affinity. Structural and functional analyses demonstrated that proteasomal cleavage 'preferences' modulated the number and length of epitope-containing peptides, thereby affecting the response avidity and clonality of T cells. Cleavage patterns were affected by both flanking and intraepitope CTL-escape mutations. Our analyses show that antigen processing shapes CTL response hierarchies and that viral evolution modifies cleavage patterns and suggest strategies for in vitro vaccine optimization.

year	journal	country	edition	language
2016-07-28	RETROVIROLOGY

10.1186/1742-4690-6-s3-p252 http://ora.ox.ac.uk/objects/uuid:8a2e9bae-d0d0-47a7-8424-c16c4f410c3a