Characterizing the binding motifs of 11 common human HLA-DP and HLA-DQ molecules using NNAlign
Article first published online: 1 JUN 2012
© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd
Volume 136, Issue 3, pages 306–311, July 2012
How to Cite
Andreatta, M. and Nielsen, M. (2012), Characterizing the binding motifs of 11 common human HLA-DP and HLA-DQ molecules using NNAlign. Immunology, 136: 306–311. doi: 10.1111/j.1365-2567.2012.03579.x
- Issue published online: 1 JUN 2012
- Article first published online: 1 JUN 2012
- Accepted manuscript online: 21 FEB 2012 01:45PM EST
- Received 22 December 2011; revised 6 February 2012; accepted 14 February 2012.
- binding motif;
- MHC class II
Compared with HLA-DR molecules, the specificities of HLA-DP and HLA-DQ molecules have only been studied to a limited extent. The description of the binding motifs has been mostly anecdotal and does not provide a quantitative measure of the importance of each position in the binding core and the relative weight of different amino acids at a given position. The recent publication of larger data sets of peptide-binding to DP and DQ molecules opens the possibility of using data-driven bioinformatics methods to accurately define the binding motifs of these molecules. Using the neural network-based method NNAlign, we characterized the binding specificities of five HLA-DP and six HLA-DQ among the most frequent in the human population. The identified binding motifs showed an overall concurrence with earlier studies but revealed subtle differences. The DP molecules revealed a large overlap in the pattern of amino acid preferences at core positions, with conserved hydrophobic/aromatic anchors at P1 and P6, and an additional hydrophobic anchor at P9 in some variants. These results confirm the existence of a previously hypothesized supertype encompassing the most common DP alleles. Conversely, the binding motifs for DQ molecules appear more divergent, displaying unconventional anchor positions and in some cases rather unspecific amino acid preferences.