Differential binding of pyruvate dehydrogenase complex-E2 epitopes by DRB1*08:01 and DRB1*11:01 Is predicted by their structural motifs and correlates with disease risk.

DRB1*08:01 (DR0801) and DRB1*11:01 (DR1101) are highly homologous alleles that have opposing effects on susceptibility to primary biliary cirrhosis (PBC). DR0801 confers risk and shares a key feature with other HLA class II alleles that predispose to autoimmunity: a nonaspartic acid at beta57. DR1101 is associated with protection from PBC, and its sequence includes an aspartic acid at beta57.

Frequency of epitope-specific naive CD4(+) T cells correlates with immunodominance in the human memory repertoire.

The frequency of epitope-specific naive CD4(+) T cells in humans has not been extensively examined. In this study, a systematic approach was used to examine the frequency of CD4(+) T cells that recognize the protective Ag of Bacillus anthracis in both anthrax vaccine-adsorbed vaccinees and nonvaccinees with HLA-DRB1*01:01 haplotypes. Three epitopes were identified that had distinct degrees of immunodominance in subjects that had received the vaccine.

DRB1*12:01 presents a unique subset of epitopes by preferring aromatics in pocket 9.

This study characterized the unique peptide-binding characteristics of HLA-DRB1*12:01 (DR1201), an allele studied in the context of various autoimmune diseases, using a peptide competition assay and structural modeling. After defining Influenza A/Puerto Rico/8/34 Matrix Protein M1 (H1MP) 40-54 as a DR1201 restricted epitope, the critical anchor residues within this sequence were confirmed by measuring the relative binding of peptides with non-conservative substitutions in competition with biotin labeled H1MP(40-54) peptide. Based on this information, a set of peptides was designed with single amino acid substitutions at these anchor positions.

Assessment of seasonal influenza A virus-specific CD4 T-cell responses to 2009 pandemic H1N1 swine-origin influenza A virus.

Very limited evidence has been reported to show human adaptive immune responses to the 2009 pandemic H1N1 swine-origin influenza A virus (S-OIV). We studied 17 S-OIV peptides homologous to immunodominant CD4 T epitopes from hemagglutinin (HA), neuraminidase (NA), nuclear protein (NP), M1 matrix protein (MP), and PB1 of a seasonal H1N1 strain. We concluded that 15 of these 17 S-OIV peptides would induce responses of seasonal influenza virus-specific T cells.

H5N1 strain-specific hemagglutinin CD4+ T cell epitopes restricted by HLA DR4.

CD4+ T cells play a pivotal role in the viral immunity, and as such identification of unique strain-specific HLA class II restricted epitopes is essential for monitoring cellular strain-specific viral immunity. Using Tetramer-Guided Epitope Mapping technique, we identified HLA-DR0401 restricted HA epitopes that are strain-specific to H5N1 virion. Two immunodominant epitopes H5HA(441-460) and H5HA(57-76) were identified from in vitro stimulated human PBMC.