Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes.

Previous studies have attempted to define human leukocyte antigen (HLA) class II supertypes, analogous to the case for class I, on the basis of shared peptide-binding motifs or structure. In the present study, we determined the binding capacity of a large panel of non-redundant peptides for a set of 27 common HLA DR, DQ, and DP molecules. The measured binding data were then used to define class II supertypes on the basis of shared binding repertoires.

Divergent motifs but overlapping binding repertoires of six HLA-DQ molecules frequently expressed in the worldwide human population.

Knowledge of the binding repertoires and specificities of HLA-DQ molecules is somewhat limited and contradictory, partly because of the scarcity of reports addressing some of the most common molecules and possibly because of the diversity of the techniques used. In this paper, we report the development of high-throughput binding assays for the six most common DQ molecules in the general worldwide population. Using comprehensive panels of single substitution analogs of specific ligands, we derived detailed binding motifs for DQA1*0501/DQB1*0301, DQA1*0401/DQB1*0402, and DQA1*0101/DQB1*0501 and more detailed motifs for DQA1*0501/DQB1*0201, DQA1*0301/DQB1*0302, and DQA1*0102/DQB1*0602, previously characterized on the basis of sets of eluted ligands and/or limited sets of substituted peptides.

Five HLA-DP molecules frequently expressed in the worldwide human population share a common HLA supertypic binding specificity.

Compared with DR and DQ, knowledge of the binding repertoires and specificities of HLA-DP alleles is somewhat limited. However, a growing body of literature has indicated the importance of DP-restricted responses in the context of cancer, allergy, and infectious disease. In the current study, we developed high-throughput binding assays for the five most common HLA-DPB1 alleles in the general worldwide population.

Con-Struct Map: a comparative contact map analysis tool.

Unlabelled: Con-Struct Map is a graphical tool for the comparative study of protein structures. The tool detects potential conserved residue contacts shared by multiple protein structures by superimposing their contact maps according to a multiple structure alignment. In general, Con-Struct Map allows the study of structural changes resulting from, e.

High-throughput identification of interacting protein-protein binding sites.

Background: With the advent of increasing sequence and structural data, a number of methods have been proposed to locate putative protein binding sites from protein surfaces. Therefore, methods that are able to identify whether these binding sites interact are needed.

Results: We have developed a new method using a machine learning approach to detect if protein binding sites, once identified, interact with each other.

Exploiting sequence and structure homologs to identify protein-protein binding sites.

A rapid increase in the number of experimentally derived three-dimensional structures provides an opportunity to better understand and subsequently predict protein-protein interactions. In this study, structurally conserved residues were derived from multiple structure alignments of the individual components of known complexes and the assigned conservation score was weighted based on the crystallographic B factor to account for the structural flexibility that will result in a poor alignment. Sequence profile and accessible surface area information was then combined with the conservation score to predict protein-protein binding sites using a Support Vector Machine (SVM).