Extensive HLA class I allele promiscuity among viral CTL epitopes

Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I‐restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well‐defined viral epitopes were tested in 100 subjects regardless of the individuals’ HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I‐restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I‐restricted antigen presentation and vaccine development.

[1]  David Heckerman,et al.  A Statistical Framework for Modeling HLA-Dependent T Cell Response Data , 2007, PLoS Comput. Biol..

[2]  D. Heckerman,et al.  Founder Effects in the Assessment of HIV Polymorphisms and HLA Allele Associations , 2007, Science.

[3]  B. Walker,et al.  Differential selection pressure exerted on HIV by CTL targeting identical epitopes but restricted by distinct HLA alleles from the same HLA supertype , 2006, The Journal of Immunology.

[4]  John Sidney,et al.  Impact of HLA-B Alleles, Epitope Binding Affinity, Functional Avidity, and Viral Coinfection on the Immunodominance of Virus-Specific CTL Responses1 , 2006, The Journal of Immunology.

[5]  E. Rosenberg,et al.  Expansion of HIV-specific CD4+ and CD8+ T cells by dendritic cells transfected with mRNA encoding cytoplasm- or lysosome-targeted Nef. , 2006, Blood.

[6]  P. Coulie,et al.  Identification of effector‐memory CMV‐specific T lymphocytes that kill CMV‐infected target cells in an HLA‐E‐restricted fashion , 2005, European journal of immunology.

[7]  G. Pape,et al.  Minimal T-Cell-Stimulatory Sequences and Spectrum of HLA Restriction of Immunodominant CD4+ T-Cell Epitopes within Hepatitis C Virus NS3 and NS4 Proteins , 2005, Journal of Virology.

[8]  Todd M. Allen,et al.  HLA-B63 Presents HLA-B57/B58-Restricted Cytotoxic T-Lymphocyte Epitopes and Is Associated with Low Human Immunodeficiency Virus Load , 2005, Journal of Virology.

[9]  C. Brander,et al.  Simultaneous assessment of cytotoxic T lymphocyte responses against multiple viral infections by combined usage of optimal epitope matrices, anti- CD3 mAb T-cell expansion and "RecycleSpot" , 2005, Journal of Translational Medicine.

[10]  Andrew K. Sewell,et al.  Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA , 2005, The Journal of experimental medicine.

[11]  Bette Korber,et al.  Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA , 2004, Nature.

[12]  M. Fernandez-Vina,et al.  Identification of a Human HLA-E-Restricted CD8+ T Cell Subset in Volunteers Immunized with Salmonella enterica Serovar Typhi Strain Ty21a Typhoid Vaccine1 , 2004, The Journal of Immunology.

[13]  D. Katzenstein,et al.  Novel and Promiscuous CTL Epitopes in Conserved Regions of Gag Targeted by Individuals with Early Subtype C HIV Type 1 Infection from Southern Africa1 , 2004, The Journal of Immunology.

[14]  L. Moretta,et al.  HLA-E-restricted recognition of human cytomegalovirus by a subset of cytolytic T lymphocytes. , 2004, Human immunology.

[15]  E. Rosenberg,et al.  Comprehensive Analysis of Human Immunodeficiency Virus Type 1-Specific CD4 Responses Reveals Marked Immunodominance of gag and nef and the Presence of Broadly Recognized Peptides , 2004, Journal of Virology.

[16]  F. M. Marincola,et al.  Consistent Cytotoxic-T-Lymphocyte Targeting of Immunodominant Regions in Human Immunodeficiency Virus across Multiple Ethnicities , 2004, Journal of Virology.

[17]  O. Lund,et al.  Definition of supertypes for HLA molecules using clustering of specificity matrices , 2004, Immunogenetics.

[18]  M. Tanimoto,et al.  Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles. , 2004, Blood.

[19]  Judy Lieberman,et al.  Mapping cross-clade HIV-1 vaccine epitopes using a bioinformatics approach. , 2003, Vaccine.

[20]  Rajiv Khanna,et al.  Promiscuous CTL Recognition of Viral Epitopes on Multiple Human Leukocyte Antigens: Biological Validation of the Proposed HLA A24 Supertype 1 , 2003, The Journal of Immunology.

[21]  B. Korber,et al.  Cross-reactive CD8+ T cell epitopes identified in US adolescent minorities. , 2003, Journal of acquired immune deficiency syndromes.

[22]  C. Rooney,et al.  Identification of a Naturally Processed HLA-DR–Restricted T-Helper Epitope in Epstein-Barr Virus Nuclear Antigen Type 1 , 2003, Journal of immunotherapy.

[23]  J. Reidhaar-Olson,et al.  The use of bioinformatics for identifying class II-restricted T-cell epitopes. , 2003, Methods.

[24]  D. Strick,et al.  Comprehensive Epitope Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T-Cell Responses Directed against the Entire Expressed HIV-1 Genome Demonstrate Broadly Directed Responses, but No Correlation to Viral Load , 2003, Journal of Virology.

[25]  J. Belisle,et al.  HLA-E–dependent Presentation of Mtb-derived Antigen to Human CD8+ T Cells , 2002, The Journal of experimental medicine.

[26]  I. Messaoudi,et al.  Direct Link Between mhc Polymorphism, T Cell Avidity, and Diversity in Immune Defense , 2002, Science.

[27]  Takamasa Ueno,et al.  Single T Cell Receptor-Mediated Recognition of an Identical HIV-Derived Peptide Presented by Multiple HLA Class I Molecules1 , 2002, The Journal of Immunology.

[28]  C. Moore,et al.  Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level , 2002, Science.

[29]  B. Walker,et al.  Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi's sarcoma-associated herpesvirus kaposin protein. , 2001, The Journal of infectious diseases.

[30]  J. Altman,et al.  An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected Thais. , 2001, AIDS research and human retroviruses.

[31]  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.

[32]  John Sidney,et al.  HLA-DR-Promiscuous T Cell Epitopes from Plasmodium falciparum Pre-Erythrocytic-Stage Antigens Restricted by Multiple HLA Class II Alleles1 2 , 2000, The Journal of Immunology.

[33]  J. Sidney,et al.  Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism , 1999, Immunogenetics.

[34]  H. Rammensee,et al.  SYFPEITHI: database for MHC ligands and peptide motifs , 1999, Immunogenetics.

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

[36]  A Sette,et al.  Identification of HLA-A3 and -B7-restricted CTL response to hepatitis C virus in patients with acute and chronic hepatitis C. , 1999, Journal of immunology.

[37]  L. Mitchell,et al.  A new categorization of HLA DR alleles on a functional basis. , 1998, Human immunology.

[38]  W. Pichler,et al.  Who is right? Or, how to judge the disagreement about HLA restriction of Nef peptides. , 1998, AIDS research and human retroviruses.

[39]  B. Walker,et al.  Degenerate and promiscuous recognition by CTL of peptides presented by the MHC class I A3-like superfamily: implications for vaccine development. , 1997, Journal of immunology.

[40]  R W Chesnut,et al.  Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis. , 1997, The Journal of clinical investigation.

[41]  R W Chesnut,et al.  Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles. , 1997, Immunity.

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

[43]  A. Toubert,et al.  Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen, a candidate autoantigen in birdshot retinopathy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[44]  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.

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

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

[47]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[48]  Sutton,et al.  The HLA-class I Restricted CTL Response in HIV-1 Infection : Identification of Optimal Epitopes , 1995 .

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

[50]  K. Parker,et al.  Sequence motifs important for peptide binding to the human MHC class I molecule, HLA-A2. , 1992, Journal of immunology.

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

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

[53]  E. Pamer,et al.  Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes , 1991, Nature.

[54]  C Oseroff,et al.  On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs. , 1991, Journal of immunology.

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

[56]  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.