Refined peptide HLA-B*3501 binding motif reveals differences in 9-mer to 11-mer peptide binding

Abstract HLA-B*3501 is associated with subacute thyroiditis and fast progression of AIDS. An important prerequisite to investigate the T-cell recognition of HLA-B*3501-restricted antigens is the characterization of peptide-HLA-B*3501 interactions. In this study, peptide-HLA-B*3501 interactions were determined in quantitative peptide binding assays. The results were statistically analyzed to evaluate the influence of both anchor and nonanchor positions and the predictability of peptide binding. The binding data demonstrated that all anchor residues at position 2 and the C-terminus found in 9-mers functioned equally as anchors in 10-mers and 11-mers. These minimum requirements of peptide binding were refined by assessing positive and negative effects of nonanchor residues. Aliphatic hydrophobic residues at positions 3, 5, and 8 of 10-mers and position 3 of 11-mers significantly enhanced HLA-B*3501 binding. Similar effects rendered aromatic, bulky residues, acidic or polar residues of 11-mers at position 1 as well as at positions 4, 8, and 10, respectively. Negative effects were observed for residues carrying positively charged side-chains at position 7 of 11-mers. The refined HLA-B*3501 peptide binding motifs enhanced the identification of potential T-cell epitopes. The disparity between positive effects at the middle and C-terminal part (positions 5 – 8 and 10) of 11-mers and shorter peptides supports the extrusion of 11-mer residues at positions 5, 6, and 7, away from the HLA-B*3501 binding cleft.

[1]  R. Winchester,et al.  HLA-B35 is associated with accelerated progression to AIDS. , 1992, Journal of acquired immune deficiency syndromes.

[2]  K. Parker,et al.  Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. , 1994, Journal of immunology.

[3]  H. Ljunggren,et al.  Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism , 1985, The Journal of experimental medicine.

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

[5]  R. Winchester,et al.  Grouping HLA-B locus serologic specificities according to shared structural motifs suggests that different peptide-anchoring pockets may have contrasting influences on the course of HIV-1 infection. , 1995, Human immunology.

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

[7]  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.

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

[9]  A Sette,et al.  Naturally processed peptides longer than nine amino acid residues bind to the class I MHC molecule HLA-A2.1 with high affinity and in different conformations. , 1994, Journal of immunology.

[10]  D I Stuart,et al.  An altered position of the alpha 2 helix of MHC class I is revealed by the crystal structure of HLA-B*3501. , 1996, Immunity.

[11]  H. Rammensee,et al.  MHC molecules as peptide receptors. , 1993, Current opinion in immunology.

[12]  Dean R. Madden,et al.  The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC , 1992, Cell.

[13]  C. Schönbach,et al.  Fine tuning of peptide binding to HLA-B*3501 molecules by nonanchor residues. , 1995, Journal of immunology.

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

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

[16]  H. Rammensee,et al.  Chemistry of peptides associated with MHC class I and class II molecules. , 1995, Current opinion in immunology.

[17]  S Ferrone,et al.  HLA-B*3501-peptide interactions: role of anchor residues of peptides in their binding to HLA-B*3501 molecules. , 1994, International immunology.

[18]  Edward J. Collins,et al.  Three-dimensional structure of a peptide extending from one end of a class I MHC binding site , 1994, Nature.

[19]  M. Bednarek,et al.  Recognition by HLA-A2-restricted cytotoxic T lymphocytes of endogenously generated and exogenously provided synthetic peptide analogues of the influenza A virus matrix protein. , 1993, Human immunology.

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

[21]  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.

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

[23]  D. B. Amos,et al.  A monoclonal antibody directed against the HLA-Bw6 epitope. , 1982, Journal of immunology.

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

[25]  S. H. van der Burg,et al.  Immunogenicity of peptides bound to MHC class I molecules depends on the MHC-peptide complex stability. , 1996, Journal of immunology.

[26]  A. Guay,et al.  Susceptibility to subacute thyroiditis is genetically influenced: familial occurrence in identical twins. , 1991, Thyroid : official journal of the American Thyroid Association.

[27]  V. Gnau,et al.  Peptide motifs of HLA-B51, -B52 and -B78 molecules, and implications for Behćet's disease. , 1995, International immunology.

[28]  Hidde L. Ploegh,et al.  Empty MHC class I molecules come out in the cold , 1990, Nature.

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