Predictable αβ T-Cell Receptor Selection toward an HLA-B*3501-Restricted Human Cytomegalovirus Epitope

ABSTRACT Human cytomegalovirus (HCMV) elicits a very large burden on the immune system, with approximately one in ten T cells being reserved solely to manage this infection. However, information on the clonotypic composition of these vast T-cell populations is limited. In this study, we sequenced 116 T-cell receptor (TcR) α/β-chains specific for the highly immunogenic HLA-B*3501-resticted epitope IPSINVHHY from the pp65 antigen. Interestingly, T cells recovered from all donors bore an identical or near-identical TRBV28/TRBJ1-4/TRAV17/TRAJ33 TcR. The ability to predict the responding αβ TcR repertoire before viral infection should prove a powerful tool for basic and clinical immunology.

[1]  R. Pass,et al.  Epidemiology and transmission of cytomegalovirus. , 1985, The Journal of infectious diseases.

[2]  G. Cloud,et al.  Cytomegalovirus infection in sexually active adolescents. , 1991, The Journal of infectious diseases.

[3]  S. Riddell,et al.  Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. , 1992, Science.

[4]  M. Bevan,et al.  Alkali hydrolysis of recombinant proteins allows for the rapid identification of class I MHC-restricted CTL epitopes. , 1993, Journal of immunology.

[5]  S. Riddell,et al.  Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. , 1995, The New England journal of medicine.

[6]  M. Weekes,et al.  The Memory Cytotoxic T-Lymphocyte (CTL) Response to Human Cytomegalovirus Infection Contains Individual Peptide-Specific CTL Clones That Have Undergone Extensive Expansion In Vivo , 1999, Journal of Virology.

[7]  A. Casrouge,et al.  A Direct Estimate of the Human αβ T Cell Receptor Diversity , 1999 .

[8]  T. Schumacher,et al.  Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1. , 2000, Immunity.

[9]  B. Johansson,et al.  Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study , 2001, Mechanisms of Ageing and Development.

[10]  P. Moss,et al.  Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals1 , 2002, The Journal of Immunology.

[11]  B. Johansson,et al.  Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study , 2002, Experimental Gerontology.

[12]  P. Moss,et al.  Comparative analysis of CD8+ T cell responses against human cytomegalovirus proteins pp65 and immediate early 1 shows similarities in precursor frequency, oligoclonality, and phenotype. , 2002, The Journal of infectious diseases.

[13]  J. Whisstock,et al.  A Structural Basis for the Selection of Dominant αβ T Cell Receptors in Antiviral Immunity , 2003 .

[14]  D. Voehringer,et al.  Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1) , 2003, Experimental Gerontology.

[15]  Ettore Appella,et al.  A correlation between TCR Valpha docking on MHC and CD8 dependence: implications for T cell selection. , 2003, Immunity.

[16]  David I Stuart,et al.  A structural basis for immunodominant human T cell receptor recognition , 2003, Nature Immunology.

[17]  P. Moss,et al.  Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines , 2003, The Lancet.

[18]  G. Pawelec,et al.  Dysfunctional CMV-specific CD8+ T cells accumulate in the elderly , 2004, Experimental Gerontology.

[19]  Richard A Koup,et al.  T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. , 2004, Immunity.

[20]  S. Kalams,et al.  Limited T Cell Receptor Diversity of HCV-specific T Cell Responses Is Associated with CTL Escape , 2004, The Journal of experimental medicine.

[21]  P. Moss,et al.  Herpesvirus-Specific CD8 T Cell Immunity in Old Age: Cytomegalovirus Impairs the Response to a Coresident EBV Infection1 , 2004, The Journal of Immunology.

[22]  R. Khanna,et al.  Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. , 2004, The Lancet. Infectious diseases.

[23]  M. Bonneville,et al.  Selection of T Cell Clones Expressing High-Affinity Public TCRs within Human Cytomegalovirus-Specific CD8 T Cell Responses1 , 2005, The Journal of Immunology.

[24]  S. Migueles,et al.  Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses , 2005, The Journal of experimental medicine.

[25]  Louis J. Picker,et al.  Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects , 2005, The Journal of experimental medicine.

[26]  Natalie A Borg,et al.  T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I–bound peptide , 2005, Nature Immunology.

[27]  R. Webby,et al.  Lack of prominent peptide–major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations , 2005, Nature Immunology.

[28]  O. Korsgren,et al.  T Cell Control of Primary and Latent Cytomegalovirus Infections in Healthy Subjects , 2005, Journal of Clinical Immunology.

[29]  TCRα Genes Direct MHC Restriction in the Potent Human T Cell Response to a Class I-Bound Viral Epitope1 , 2006, The Journal of Immunology.

[30]  Robyn L Stanfield,et al.  How TCRs bind MHCs, peptides, and coreceptors. , 2006, Annual review of immunology.

[31]  Chung-Che Chang,et al.  Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals , 2006, Nature Medicine.

[32]  John J Miles,et al.  Engineered T cell receptors and their potential in molecular medicine. , 2006, Current medicinal chemistry.

[33]  C. Soderberg-Naucler.  Human cytomegalovirus persists in its host and attacks and avoids elimination by the immune system. , 2006, Critical reviews in immunology.

[34]  P. Doherty,et al.  Structural determinants of T-cell receptor bias in immunity , 2006, Nature Reviews Immunology.

[35]  Nicholas A Williamson,et al.  A T cell receptor flattens a bulged antigenic peptide presented by a major histocompatibility complex class I molecule , 2007, Nature Immunology.

[36]  J. McCluskey,et al.  The impact of HLA‐B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV , 2007, European journal of immunology.