Population of the HLA ligand database.

We have established an HLA ligand database to provide scientists and clinicians with access to Major Histocompatibility Complex (MHC) class I and II motif and ligand data. The HLA Ligand Database is available on the world wide web at http://hlaligand.ouhsc.edu and contains ligands that have been published in peer-reviewed journals. HLA peptide datasets prove useful in several areas: ligands are important as targets for various immune responses while algorithms built upon ligand datasets allow identification of new peptides without time-consuming experimental procedures. A review of the HLA class I ligands in the database identifies strengths and deficiencies in the database and, therefore, the utility of the dataset for identifying new peptides. For instance, 212 HLA-A phenotypes exist of which 23 have a motif determined and 43 have peptides characterized. In terms of number of ligands, HLA-A*0201 has 258 characterized ligands, A*1101 has 25 peptides, while the remaining two-thirds of the HLA-A phenotypes have less than 10 associated peptide sequences. Characterization of ligands and motifs remains roughly the same at the HLA-B locus while the peptides of the HLA-C locus tend to be less characterized. These data show that 74% of HLA class I molecules do not have ligands represented in the database and thus algorithms based on the dataset could not predict ligands for a majority of the US population. Building upon this dataset and knowledge of HLA allelic frequencies, it is possible to plan a systematic expansion of the HLA class I ligand database to better identify ligands useful throughout the population.

[1]  P. Parham,et al.  Nature of polymorphism in HLA-A, -B, and -C molecules. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[2]  E. Rosenberg,et al.  Rapid Definition of Five Novel HLA-A∗3002-Restricted Human Immunodeficiency Virus-Specific Cytotoxic T-Lymphocyte Epitopes by Elispot and Intracellular Cytokine Staining Assays , 2001, Journal of Virology.

[3]  R. Germain Immunology: The ins and outs of antigen processing and presentations , 1986, Nature.

[4]  Ilan Beer,et al.  Analysis of endogenous peptides bound by soluble MHC class I molecules: a novel approach for identifying tumor‐specific antigens , 2002, European journal of immunology.

[5]  Mark Lindsey,et al.  Large-scale production of class I bound peptides: assigning a signature to HLA-B*1501 , 1997, Immunogenetics.

[6]  Hans-Georg Rammensee,et al.  MHC ligands and peptide motifs: first listing , 2004, Immunogenetics.

[7]  J. Galán,et al.  Induction of specific CD8+ memory T cells and long lasting protection following immunization with Salmonella typhimurium expressing a lymphocytic choriomeningitis MHC class I-restricted epitope. , 2001, Vaccine.

[8]  P. Parham,et al.  Guilt by association: HLA-B27 and ankylosing spondylitis. , 1990, Immunology today.

[9]  J. Altman,et al.  Peptide-MHC Class I Tetrameric Complexes Display Exquisite Ligand Specificity1 , 2000, The Journal of Immunology.

[10]  Mark Lindsey,et al.  Complexity among constituents of the HLA-B*1501 peptide motif , 1998, Immunogenetics.

[11]  F. Brodsky,et al.  Human pathogen subversion of antigen presentation , 1999, Immunological reviews.

[12]  V. Gnau,et al.  Peptide motifs of HLA-A1,-A11,-A31, and-A33 molecules , 1994, Immunogenetics.

[13]  M F del Guercio,et al.  Several HLA alleles share overlapping peptide specificities. , 1995, Journal of immunology.

[14]  C. Sylvester-Hvid,et al.  Efficient assembly of recombinant major histocompatibility complex class I molecules with preformed disulfide bonds , 2001, European journal of immunology.

[15]  J. Shabanowitz,et al.  The peptide recognized by HLA-A68.2-restricted, squamous cell carcinoma of the lung-specific cytotoxic T lymphocytes is derived from a mutated elongation factor 2 gene. , 1998, Cancer research.

[16]  C. Herberts,et al.  A single naturally processed measles virus peptide fully dominates the HLA‐A*0201‐associated peptide display and is mutated at its anchor position in persistent viral strains , 2000, European journal of immunology.

[17]  P. Cresswell,et al.  Co-localization of molecules involved in antigen processing and presentation in an early endocytic compartment , 1990, Nature.

[18]  W. Hildebrand,et al.  HLA-B15 peptide ligands are preferentially anchored at their C termini. , 1999, Journal of immunology.

[19]  P. Parham,et al.  Overlap in the repertoires of peptides bound in vivo by a group of related class I HLA-B allotypes , 1995, Current Biology.

[20]  H. Rammensee,et al.  Peptide motifs of closely related HLA class I molecules encompass substantial differences , 1992, European journal of immunology.

[21]  P. Brossart,et al.  Direct identification of major histocompatibility complex class I-bound tumor-associated peptide antigens of a renal carcinoma cell line by a novel mass spectrometric method. , 1998, Cancer research.

[22]  W. Pichler,et al.  Perspectives: towards a peptide-based vaccine against hepatitis C virus. , 2001, Molecular immunology.

[23]  Andrew J. McMichael,et al.  Common West African HLA antigens are associated with protection from severe malaria , 1991, Nature.

[24]  W. Hildebrand,et al.  C-terminal epitope tagging facilitates comparative ligand mapping from MHC class I positive cells. , 2000, Human immunology.

[25]  R. Koup,et al.  Monitoring HIV-specific CD8+ T cell responses by intracellular cytokine production. , 2001, Immunology letters.

[26]  M. Owais,et al.  Fusogenic potential of prokaryotic membrane lipids. , 2001 .

[27]  K. Cao,et al.  Analysis of the frequencies of HLA-A, B, and C alleles and haplotypes in the five major ethnic groups of the United States reveals high levels of diversity in these loci and contrasting distribution patterns in these populations. , 2001, Human immunology.

[28]  D. Rognan,et al.  Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins. , 1999, Journal of medicinal chemistry.

[29]  J. Sidney,et al.  Peptide binding to the most frequent HLA-A class I alleles measured by quantitative molecular binding assays. , 1994, Molecular immunology.

[30]  J. Goedert,et al.  HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. , 1999, Science.

[31]  D. Nixon,et al.  Identification of subdominant cytotoxic T lymphocyte epitopes encoded by autologous HIV type 1 sequences, using dendritic cell stimulation and computer-driven algorithm. , 2000, AIDS research and human retroviruses.

[32]  R. Henderson,et al.  Characteristics of endogenous peptides eluted from the class I MHC molecule HLA-B7 determined by mass spectrometry and computer modeling. , 1993, Journal of immunology.

[33]  A Sette,et al.  Definition of specific peptide motifs for four major HLA-A alleles. , 1994, Journal of immunology.

[34]  A. Burny,et al.  Cytotoxic T lymphocytes specific for HIV-1 gp160 antigen and synthetic P18IIIB peptide in an HLA-A11-immunized individual. , 1994, AIDS research and human retroviruses.

[35]  R. Henderson,et al.  Recognition of human melanoma cells by HLA-A2.1-restricted cytotoxic T lymphocytes is mediated by at least six shared peptide epitopes. , 1993, Journal of immunology.

[36]  Vladimir Brusic,et al.  Prediction of promiscuous peptides that bind HLA class I molecules , 2002, Immunology and cell biology.