HLA class II peptide-binding-region analysis reveals funneling of polymorphism in action. 2021

Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
Department of Biochemistry and Biotechnology, Laboratory of Genetics, Comparative and Evolutionary Biology, University of Thessaly, Viopolis, Mezourlo, 41500, Larisa, Greece.

HLA-class II proteins hold important roles in key physiological processes. The purpose of this study was to compile all class II alleles reported in human population and investigate patterns in pocket variants and their combinations, focusing on the peptide-binding region (PBR). For this purpose, all protein sequences of DPA1, DQA1, DPB1, DQB1 and DRB1 were selected and filtered, in order to have full PBR sequences. Proportional representation was used for pocket variants while population data were also used. All pocket variants and PBR sequences were retrieved and analyzed based on the preference of amino acids and their properties in all pocket positions. The observed number of pocket variants combinations was much lower than the possible inferred, suggesting that PBR formation is under strict funneling. Also, although class II proteins are very polymorphic, in the majority of the reported alleles in all populations, a significantly less polymorphic pocket core was found. Pocket variability of five HLA class II proteins was studied revealing favorable properties of each protein. The actual PBR sequences of HLA class II proteins appear to be governed by restrictions that lead to the establishment of only a fraction of the possible combinations and the polymorphism recorded is the result of intense funneling based on function.

UI MeSH Term Description Entries
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000949 Histocompatibility Antigens Class II Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen. Antigens, Immune Response,Class II Antigens,Class II Histocompatibility Antigen,Class II Major Histocompatibility Antigen,Ia Antigens,Ia-Like Antigen,Ia-Like Antigens,Immune Response Antigens,Immune-Associated Antigens,Immune-Response-Associated Antigens,MHC Class II Molecule,MHC II Peptide,Class II Antigen,Class II Histocompatibility Antigens,Class II MHC Proteins,Class II Major Histocompatibility Antigens,Class II Major Histocompatibility Molecules,I-A Antigen,I-A-Antigen,IA Antigen,MHC Class II Molecules,MHC II Peptides,MHC-II Molecules,Antigen, Class II,Antigen, I-A,Antigen, IA,Antigen, Ia-Like,Antigens, Class II,Antigens, Ia,Antigens, Ia-Like,Antigens, Immune-Associated,Antigens, Immune-Response-Associated,I A Antigen,II Peptide, MHC,Ia Like Antigen,Ia Like Antigens,Immune Associated Antigens,Immune Response Associated Antigens,MHC II Molecules,Molecules, MHC-II,Peptide, MHC II,Peptides, MHC II
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D059866 HLA-DQ beta-Chains Transmembrane proteins that form the beta subunits of the HLA-DQ antigens. HLA Class II Histocompatibility Antigen, DQ beta Chains,HLA DQ beta Chains,beta-Chains, HLA-DQ
D020816 Amino Acid Motifs Three-dimensional protein structural elements that are composed of a combination of secondary structures. They include HELIX-LOOP-HELIX MOTIFS and ZINC FINGERS. Motifs are typically the most conserved regions of PROTEIN DOMAINS and are critical for domain function. However, the same motif may occur in proteins or enzymes with different functions. AA Motifs,Motifs, Amino Acid,Protein Motifs,Protein Structure, Supersecondary,Supersecondary Protein Structure,AA Motif,Amino Acid Motif,Motif, AA,Motif, Amino Acid,Motif, Protein,Motifs, AA,Motifs, Protein,Protein Motif,Protein Structures, Supersecondary,Supersecondary Protein Structures

Related Publications

Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
April 1987, Human immunology,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
February 2002, Tissue antigens,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
January 1997, Advances in immunology,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
October 1995, Tissue antigens,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
March 2009, Human immunology,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
January 1992, Journal of immunology (Baltimore, Md. : 1950),
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
January 1989, Cold Spring Harbor symposia on quantitative biology,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
May 1993, Archives of pathology & laboratory medicine,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
July 1990, Seminars in immunology,
Constantina A Sarri, and Themistoklis Giannoulis, and Katerina A Moutou, and Zissis Mamuris
January 1995, Tissue antigens,
Copied contents to your clipboard!