Definition of an HLA-A3-like supermotif demonstrates the overlapping peptide-binding repertoires of common HLA molecules.

An HLA-A3-like supertype (minimally comprised of products from the HLA class I alleles A3, A11, A31, A*3301, and A*6801) has been defined on the basis of (a) structural similarities in the antigen-binding groove, (b) shared main anchor peptide-binding motifs, (c) the identification of peptides cross-reacting with most or all of these molecules, and (d) the definition of an A3-like supermotif that efficiently predicts highly cross-reactive peptides. Detailed secondary anchor maps for A3, A11, A31, A*3301, and A*6801 are also described. The biologic relevance of the A3-like supertype is indicated by the fact that high frequencies of the A3-like supertype alleles are conserved in all major ethnic groups. Because A3-like supertype alleles are found in most major HLA evolutionary lineages, possibly a reflection of common ancestry, the A3-like supermotif might in fact represent a primeval human HLA class I peptide-binding specificity. It is also possible that these phenomena might be related to optimal exploitation of the peptide specificity by human TAP molecules. The grouping of HLA alleles into supertypes on the basis of their overlapping peptide-binding repertoires represents an alternative to serologic or phylogenetic classification.

[1]  J. Rothbard,et al.  Degenerate binding of immunogenic peptides to HLA-DR proteins on B cell surfaces. , 1990, International immunology.

[2]  M. Aidoo,et al.  Molecular analysis of the association of HLA-B53 and resistance to severe malaria , 1992, Nature.

[3]  R W Chesnut,et al.  Characterization of the specificity of peptide binding to four DR haplotypes. , 1990, Journal of immunology.

[4]  S. Rowland-Jones,et al.  A sequence pattern for peptides presented to cytotoxic T lymphocytes by HLA B8 revealed by analysis of epitopes and eluted peptides , 1993, European journal of immunology.

[5]  P Parham,et al.  Evolution of class-I MHC genes and proteins: from natural selection to thymic selection. , 1990, Annual review of immunology.

[6]  William S. Lane,et al.  Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle , 1992, Nature.

[7]  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.

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

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

[10]  A. Townsend,et al.  Antigen recognition by class I-restricted T lymphocytes. , 1989, Annual review of immunology.

[11]  D. Wiley,et al.  The antigenic identity of peptide-MHC complexes: A comparison of the conformations of five viral peptides presented by HLA-A2 , 1993, Cell.

[12]  H. Grey,et al.  In vitro induction of primary, antigen-specific CTL from human peripheral blood mononuclear cells stimulated with synthetic peptides. , 1995, Molecular immunology.

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

[14]  W R Mayr,et al.  Nomenclature for factors of the HLA system, 1995. , 1995, Tissue antigens.

[15]  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.

[16]  B. Malissen,et al.  Structural and genetic analyses of HLA class I molecules using monoclonal xenoantibodies. , 2008, Tissue antigens.

[17]  P. Stastny,et al.  DNA typing for HLA class I alleles: I. Subsets of HLA-A2 and of -A28. , 1992, Human immunology.

[18]  R. Tampé,et al.  A sequential model for peptide binding and transport by the transporters associated with antigen processing. , 1994, Immunity.

[19]  R. Zinkernagel,et al.  Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system , 1974, Nature.

[20]  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.

[21]  H. Ploegh,et al.  Substrate specificity of allelic variants of the TAP peptide transporter. , 1994, Immunity.

[22]  A. Vitiello,et al.  Development of a lipopeptide-based therapeutic vaccine to treat chronic HBV infection. I. Induction of a primary cytotoxic T lymphocyte response in humans. , 1995, The Journal of clinical investigation.

[23]  C. Barnstable,et al.  Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis , 1978, Cell.

[24]  A Sette,et al.  Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. , 1994, Journal of immunology.

[25]  T. Elliott,et al.  Peptide selection by class I molecules of the major histocompatibility complex , 1993, Current Biology.

[26]  P. Cresswell,et al.  Human transporters associated with antigen processing possess a promiscuous peptide-binding site. , 1994, Immunity.

[27]  P. Cresswell,et al.  Evidence that transporters associated with antigen processing translocate a major histocompatibility complex class I-binding peptide into the endoplasmic reticulum in an ATP-dependent manner. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

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

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

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

[31]  B. Guy,et al.  Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein. , 1991, Journal of immunology.

[32]  J. Neefjes,et al.  Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. , 1993, Science.

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

[34]  K. Parker,et al.  Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8. , 1994, Journal of immunology.

[35]  F. Greenwood,et al.  THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. , 1963, The Biochemical journal.

[36]  B. Moss,et al.  Mapping the fine specificity of a cytolytic T cell response to HIV-1 nef protein. , 1990, Journal of immunology.

[37]  N. Suciu-Foca,et al.  Naturally processed HLA class I bound peptides from c-myc-transfected cells reveal allele-specific motifs. , 1993, Journal of immunology.

[38]  J. Sidney,et al.  Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules , 1993, Cell.

[39]  Hans-Georg Rammensee,et al.  Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells , 1990, Nature.

[40]  G Hermanson,et al.  Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype. , 1995, Journal of immunology.

[41]  R. Tosi,et al.  HLA-A2-binding peptides cross-react not only within the A2 subgroup but also with other HLA-A-locus allelic products. , 1994, Human immunology.

[42]  Antonio Lanzavecchia,et al.  Universally immunogenic T cell epitopes: promiscuous binding to human MHC class II and promiscuous recognition by T cells , 1989, European journal of immunology.

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

[44]  P. Terasaki,et al.  The HLA Complex , 1985 .

[45]  C. Bordignon,et al.  Characterization of natural peptide ligands for HLA-B*4402 and -B*4403: implications for peptide involvement in allorecognition of a single amino acid change in the HLA-B44 heavy chain. , 1994, Tissue antigens.

[46]  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.

[47]  K. Tadokoro,et al.  Sequences of four splits of HLA-A10 group. Implications for serologic cross-reactivities and their evolution. , 1994, Human immunology.

[48]  M. Lotze,et al.  Identification of human melanoma peptides recognized by class I restricted tumor infiltrating T lymphocytes. , 1993, Journal of immunology.

[49]  V. Engelhard Structure of peptides associated with MHC class I molecules. , 1994, Current opinion in immunology.

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

[51]  R M Zinkernagel,et al.  MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. , 1979, Advances in immunology.

[52]  E. Adams,et al.  The Origins of HLA‐A,B,C Polymorphism , 1995, Immunological reviews.

[53]  J. Trapani,et al.  Molecular analysis of the serologically defined HLA-Aw19 antigens. A genetically distinct family of HLA-A antigens comprising A29, A31, A32, and Aw33, but probably not A30. , 1989, Journal of immunology.

[54]  J. Neefjes,et al.  Peptide selection by MHC-encoded TAP transporters. , 1994, Current opinion in immunology.

[55]  P. Terasaki,et al.  HLA and Disease Associations , 1985, Springer New York.

[56]  F. Chisari,et al.  HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis , 1993, The Journal of experimental medicine.

[57]  Arne Svejgaard,et al.  Nomenclature for Factors of the HLA System, 1995 , 1995, Vox sanguinis.

[58]  K. Parker,et al.  HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. , 1993, Journal of immunology.