3GIV

Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance

Summary for 3GIV

• Entry DOI: 10.2210/pdb3giv/pdb
• Related: 2V2W 2V2X
• Descriptor: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, HIV-1 peptide, ... (4 entities in total)
• Functional Keywords: hiv, mhc, escape, antigen, immune recognition, disulfide bond, glycoprotein, host-virus interaction, immune response, membrane, mhc i, phosphoprotein, transmembrane, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted', immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769
• Total number of polymer chains: 6
• Total formula weight: 89723.67

Authors

Stewart-Jones, G.,Iversen, A.K.N.,Jones, E.Y. (deposition date: 2009-03-06, release date: 2009-06-30, Last modification date: 2024-10-30)

Primary citation

Tenzer, S.,Wee, E.,Burgevin, A.,Stewart-Jones, G.,Friis, L.,Lamberth, K.,Chang, C.-H.,Harndahl, M.,Weimershaus, M.,Gerstoft, J.,Akkad, N.,Klenerman, P.,Fugger, L.,Jones, E.Y.,McMichael, A.J.,Buus, S.,Schild, H.,van Endert, P.,Iversen, A.K.N.
Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance
Nat.Immunol., 10:636-646, 2009

PubMed Abstract: 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.

PubMed: 19412183
DOI: 10.1038/ni.1728

Experimental method

X-RAY DIFFRACTION (2 Å)