HLA-A3 supermotif defined by quantitative structure-activity relationship analysis.

Activation of a cytotoxic T cell requires specific binding of antigenic peptides to major histocompatibility complex (MHC) molecules. This paper reports a study of peptides binding to members of the HLA-A3 superfamily using a recently developed 2D-QSAR method, called the additive method. Four alleles with high phenotype frequency were included in the study: A*0301, A*1101, A*3101 and A*6801. The influence of each of the 20 amino acids at each position of the peptide on binding was studied. A refined A3 supertype motif was defined in the study.

[1]  D. R. Madden,et al.  Identification of self peptides bound to purified HLA-B27 , 1991, Nature.

[2]  G. Yoo,et al.  Foreign antigenic peptides delivered to the tumor as targets of cytotoxic T cells. , 2001, Journal of immunological methods.

[3]  M. Mannie.  T cell-mediated antigen presentation , 2001, Immunologic research.

[4]  Don C. Wiley,et al.  Atomic structure of a human MHC molecule presenting an influenza virus peptide , 1992, Nature.

[5]  J. Kim,et al.  Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers , 2001, Experimental & Molecular Medicine.

[6]  A Sette,et al.  Practical, biochemical and evolutionary implications of the discovery of HLA class I supermotifs. , 1996, Immunology today.

[7]  M. A. Saper,et al.  Structure of the human class I histocompatibility antigen, HLA-A2 , 1987, Nature.

[8]  Irini A. Doytchinova,et al.  JenPep: a database of quantitative functional peptide data for immunology , 2002, Bioinform..

[9]  O. Rötzschke,et al.  Consensus motifs and peptide ligands of MHC class I molecules. , 1993, Seminars in immunology.

[10]  G. Nepom,et al.  MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition. , 1999, Human immunology.

[11]  J. Sidney,et al.  Class I MHC-peptide interaction: structural and functional aspects. , 1994, Behring Institute Mitteilungen.

[12]  D. Wiley,et al.  Comparison of the P2 specificity pocket in three human histocompatibility antigens: HLA-A*6801, HLA-A*0201, and HLA-B*2705. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[13]  C DeLisi,et al.  Computational determination of side chain specificity for pockets in class I MHC molecules. , 1996, Molecular immunology.

[14]  D. Wiley,et al.  Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules. , 1994, Science.

[15]  P. A. Peterson,et al.  Emerging principles for the recognition of peptide antigens by MHC class I molecules. , 1992, Science.

[16]  H Kubinyi,et al.  Quantitative structure-activity relationships. 1. The modified Free-Wilson approach. , 1976, Journal of medicinal chemistry.

[17]  J. Gutiérrez-Ramos,et al.  The expanding B7 superfamily: Increasing complexity in costimulatory signals regulating T cell function , 2001, Nature Immunology.

[18]  A. Sette,et al.  Identification of GP100‐derived, melanoma‐specific cytotoxic T‐lymphocyte epitopes restricted by HLA‐A3 supertype molecules by primary in vitro immunization with peptide‐pulsed dendritic cells , 1998, International journal of cancer.

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

[20]  Takashi Saito,et al.  Dependence of T Cell Antigen Recognition on the Dimensions of an Accessory Receptor–Ligand Complex , 1999, The Journal of experimental medicine.

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

[22]  Bruce L. Bush,et al.  Sample-distance partial least squares: PLS optimized for many variables, with application to CoMFA , 1993, J. Comput. Aided Mol. Des..

[23]  H. Rammensee,et al.  Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules , 1991, Nature.

[24]  J. Sidney,et al.  HLA supertypes and supermotifs: a functional perspective on HLA polymorphism. , 1998, Current opinion in immunology.

[25]  M F del Guercio,et al.  Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide-binding repertoires of common HLA molecules. , 1996, Human immunology.

[26]  Limsoon Wong,et al.  FIMM, a database of functional molecular immunology , 2000, Nucleic Acids Res..

[27]  John Sidney,et al.  Identification of Novel HLA-A2-Restricted Human Immunodeficiency Virus Type 1-Specific Cytotoxic T-Lymphocyte Epitopes Predicted by the HLA-A2 Supertype Peptide-Binding Motif , 2001, Journal of Virology.

[28]  S. H. van der Burg,et al.  An HLA class I peptide-binding assay based on competition for binding to class I molecules on intact human B cells. Identification of conserved HIV-1 polymerase peptides binding to HLA-A*0301. , 1995, Human immunology.

[29]  D. Flower,et al.  Additive method for the prediction of protein-peptide binding affinity. Application to the MHC class I molecule HLA-A*0201. , 2002, Journal of proteome research.

[30]  G. Klein,et al.  An HLA-A11-specific motif in nonamer peptides derived from viral and cellular proteins. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Muñoz de la Peña,et al.  Comparative study of partial least squares and a modification of hybrid linear analysis calibration in the simultaneous spectrophotometric determination of rifampicin, pyrazinamide and isoniazid , 2001 .

[32]  D. R. Madden,et al.  The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation , 1991, Nature.

[33]  D. Wiley,et al.  Refined structure of the human histocompatibility antigen HLA-A2 at 2.6 A resolution. , 1991, Journal of molecular biology.

[34]  M. A. Saper,et al.  Specificity pockets for the side chains of peptide antigens in HLA-Aw68 , 1990, Nature.

[35]  D. Madden.  The three-dimensional structure of peptide-MHC complexes. , 1995, Annual review of immunology.

[36]  Han van de Waterbeemd,et al.  Chemometric methods in molecular design , 1995 .

[37]  Darren R. Flower,et al.  Drug design : cutting edge approaches , 2002 .

[38]  P Parham,et al.  Structure, function, and diversity of class I major histocompatibility complex molecules. , 1990, Annual review of biochemistry.

[39]  K. Parker,et al.  Endogenous peptides bound to HLA-A3 possess a specific combination of anchor residues that permit identification of potential antigenic peptides. , 1993, Proceedings of the National Academy of Sciences of the United States of America.