The many important facets of T-cell repertoire diversity

In the thymus, a diverse and polymorphic T-cell repertoire is generated by random recombination of discrete T-cell receptor (TCR)-αβ gene segments. This repertoire is then shaped by intrathymic selection events to generate a peripheral T-cell pool of self-MHC restricted, non-autoaggressive T cells. It has long been postulated that some optimal level of TCR diversity allows efficient protection against pathogens. This article focuses on several recent advances that address the required diversity for the generation of an optimal immune response.

[1]  V. Wahn,et al.  Diversity, functionality, and stability of the T cell repertoire derived in vivo from a single human T cell precursor. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[2]  G. Schönrich,et al.  Down-regulation of T cell receptors on self-reactive T cells as a novel mechanism for extrathymic tolerance induction , 1991, Cell.

[3]  R. Ahmed,et al.  Preferential Escape of Subdominant CD8+ T Cells During Negative Selection Results in an Altered Antiviral T Cell Hierarchy 1 , 2003, The Journal of Immunology.

[4]  Emmanuel Beaudoing,et al.  Size Estimate of the αβ TCR Repertoire of Naive Mouse Splenocytes1 , 2000, The Journal of Immunology.

[5]  D. Fremont,et al.  Peptide selection by an MHC H-2Kb class I molecule devoid of the central anchor ("C") pocket. , 1998, Journal of immunology.

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

[7]  R. Dyall,et al.  The critical role of a solvent-exposed residue of an MHC class I-restricted peptide in MHC-peptide binding. , 1997, International immunology.

[8]  M. Regner Cross‐reactivity in T‐cell antigen recognition , 2001, Immunology and cell biology.

[9]  Rustom Antia,et al.  Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells , 2002, The Journal of experimental medicine.

[10]  C. Benoist,et al.  The influence of invariant chain on the positive selection of single T cell receptor specificities , 1995, European journal of immunology.

[11]  Ian A Wilson,et al.  The specificity of TCR/pMHC interaction. , 2002, Current opinion in immunology.

[12]  P. Marrack,et al.  CD8+ T‐cell clones in old mice , 1997, Immunological reviews.

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

[14]  Todd M. Allen,et al.  Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef , 1999, Nature Medicine.

[15]  J. Cabaniols,et al.  Most α/β T Cell Receptor Diversity Is Due to Terminal Deoxynucleotidyl Transferase , 2001, The Journal of experimental medicine.

[16]  Mark I. Greene,et al.  Control of MHC Restriction by TCR Vα CDR1 and CDR2 , 1996, Science.

[17]  F. Mami-Chouaib,et al.  Cytotoxic T lymphocytes directed against a tumor-specific mutated antigen display similar HLA tetramer binding but distinct functional avidity and tissue distribution , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Abe,et al.  Swift Development of Protective Effector Functions in Naive Cd8+ T Cells against Malaria Liver Stages , 2001, The Journal of experimental medicine.

[19]  G. Pawelec,et al.  Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion? , 1997, Immunology today.

[20]  P. Doherty,et al.  Diversity of Epitope and Cytokine Profiles for Primary and Secondary Influenza A Virus-Specific CD8+ T Cell Responses1 , 2001, The Journal of Immunology.

[21]  P. Kourilsky,et al.  T-cell repertoires in healthy and diseased human tissues analysed by T-cell receptor beta-chain CDR3 size determination: evidence for oligoclonal expansions in tumours and inflammatory diseases. , 1995, Research in immunology.

[22]  F. Carbone,et al.  Characterization of diverse primary herpes simplex virus type 1 gB-specific cytotoxic T-cell response showing a preferential V beta bias , 1995, Journal of virology.

[23]  G. J. V. Nossal,et al.  Negative selection of lymphocytes , 1994, Cell.

[24]  J. Lieberman,et al.  A transgenic mouse model to analyze CD8(+) effector T cell differentiation in vivo. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[25]  P. Fink,et al.  Chronic modulation of the TCR repertoire in the lymphoid periphery. , 1999, Journal of immunology.

[26]  F. Burnet The cellular basis of immunology. , 1961, Japanese journal of microbiology.

[27]  M. Bevan,et al.  Increased peptide promiscuity provides a rationale for the lack of N regions in the neonatal T cell repertoire. , 1995, Immunity.

[28]  S. Turner,et al.  TCR alpha-chain usage can determine antigen-selected TCR beta-chain repertoire diversity. , 1996, Journal of immunology.

[29]  D. Mason,et al.  A very high level of crossreactivity is an essential feature of the T-cell receptor. , 1998, Immunology today.

[30]  J. Zerrahn,et al.  The MHC Reactivity of the T Cell Repertoire Prior to Positive and Negative Selection , 1997, Cell.

[31]  E. Sercarz,et al.  Limitations in plasticity of the T-cell receptor repertoire. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  H. Pircher,et al.  Qualitative and quantitative requirements for CD4+ T cell-mediated antiviral protection. , 1999, Journal of immunology.

[33]  T. Hanke,et al.  Cumulative Inhibition of NK Cells and T Cells Resulting from Engagement of Multiple Inhibitory Ly49 Receptors1 , 2001, The Journal of Immunology.

[34]  S. Tonegawa,et al.  Somatic reorganization of immunoglobulin genes during lymphocyte differentiation. , 1981, Cold Spring Harbor symposia on quantitative biology.

[35]  F. Carbone,et al.  Evidence for cooperation between TCR V region and junctional sequences in determining a dominant cytotoxic T lymphocyte response to herpes simplex virus glycoprotein B. , 1997, International immunology.

[36]  D. Woodland,et al.  Functional consequences of a T cell receptor D beta 2 and J beta 2 gene segment deletion. , 1990, Journal of immunology.

[37]  MHC class I and non-MHC-linked capacity for generating an anti-viral CTL response determines susceptibility to CTL exhaustion and establishment of virus persistence in mice. , 1994, Journal of immunology.

[38]  Mark M. Davis,et al.  T-cell antigen receptor genes and T-cell recognition , 1988, Nature.

[39]  J. Miller,et al.  Expression of two alpha chains on the surface of T cells in T cell receptor transgenic mice , 1993, The Journal of experimental medicine.

[40]  I. Messaoudi,et al.  MHC Polymorphism Can Enrich the T Cell Repertoire of the Species by Shifts in Intrathymic Selection , 2000, The Journal of Immunology.

[41]  J. Murray,et al.  How the MHC selects Th1/Th2 immunity. , 1998, Immunology today.

[42]  P. Bucher,et al.  Individuality of Ag-selected and preimmune TCR repertoires , 2001, Immunologic research.

[43]  K. Garcia,et al.  Structural basis of T cell recognition. , 1999, Annual review of immunology.

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

[45]  M. Bevan,et al.  Role of self-peptides in positively selecting the T-cell repertoire , 1990, Nature.

[46]  R. Zinkernagel,et al.  Uncertainties − discrepancies in immunology , 2002, Immunological reviews.

[47]  H. Kishi,et al.  Deletion of autospecific T cells in T cell receptor (TCR) transgenic mice spares cells with normal TCR levels and low levels of CD8 molecules , 1989, The Journal of experimental medicine.

[48]  A. Balsari,et al.  Contribution of CD4+, CD8+CD28+, and CD8+CD28- T cells to CD3+ lymphocyte homeostasis during the natural course of HIV-1 infection. , 1998, The Journal of clinical investigation.

[49]  M. Cohn,et al.  The Protection: The Unit of Humoral Immunity Selected by Evolution , 1990, Immunological reviews.

[50]  D. Schatz,et al.  Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes , 1993, The Journal of experimental medicine.

[51]  F. Delbos,et al.  Ig gene hypermutation: a mechanism is due. , 2002, Advances in immunology.

[52]  J Nikolić-Zugić,et al.  Role of self-peptides in positively selecting the T-cell repertoire. , 1990 .

[53]  J. Lieberman,et al.  Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes. , 2001, The Journal of clinical investigation.

[54]  J. Whitton,et al.  Activated and Memory CD8+ T Cells Can Be Distinguished by Their Cytokine Profiles and Phenotypic Markers1 , 2000, The Journal of Immunology.

[55]  R. Zinkernagel,et al.  Efficient immune responses in mice lacking N‐region diversity , 1995, European journal of immunology.

[56]  J. Leunissen,et al.  Definition of natural T cell antigens with mimicry epitopes obtained from dedicated synthetic peptide libraries. , 1998, Journal of immunology.

[57]  J. Berzofsky,et al.  The importance of dominant negative effects of amino acid side chain substitution in peptide-MHC molecule interactions and T cell recognition. , 1993, Journal of immunology.

[58]  M. B E R N A S C H I 1 A N D F C A S T I G L I O N E Selection of escape mutants from immune recognition during HIV infection , 2002 .

[59]  R. Welsh,et al.  Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses , 1994, The Journal of experimental medicine.

[60]  A. Smolyar,et al.  The crystal structure of a T cell receptor in complex with peptide and MHC class II. , 1999, Science.

[61]  Raymond M. Welsh,et al.  Stability and Diversity of  T Cell Receptor Repertoire Usage during Lymphocytic Choriomeningitis Virus Infection of Mice , 1998, The Journal of experimental medicine.

[62]  Kristin A. Hogquist,et al.  Receptor editing in developing T cells , 2000, Nature Immunology.

[63]  C. Benoist,et al.  Mice lacking TdT: mature animals with an immature lymphocyte repertoire. , 1993, Science.

[64]  Todd M. Allen,et al.  Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence? , 2002, Journal of Virology.

[65]  B. Malissen Glimpses at TCR trans-species crossreactivity. , 2003, Immunity.

[66]  H. Rammensee,et al.  Identification of naturally processed viral nonapeptides allows their quantification in infected cells and suggests an allele-specific T cell epitope forecast , 1991, The Journal of experimental medicine.

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

[68]  R. Zinkernagel,et al.  Discrepancy between in vitro measurable and in vivo virus neutralizing cytotoxic T cell reactivities. Low T cell receptor specificity and avidity sufficient for in vitro proliferation or cytotoxicity to peptide-coated target cells but not for in vivo protection. , 1992, Journal of immunology.

[69]  P. Kourilsky,et al.  T-cell repertoire diversity and clonal expansions in normal and clinical samples. , 1995, Immunology today.

[70]  P. Kourilsky,et al.  Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion. , 2000, Immunity.

[71]  A. McMichael,et al.  T Cell Responses and Viral Escape , 1998, Cell.

[72]  P. A. Peterson,et al.  Crystal structure of an H-2Kb-ovalbumin peptide complex reveals the interplay of primary and secondary anchor positions in the major histocompatibility complex binding groove. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[73]  K. Kikly,et al.  Evidence for a role for T cell receptors (TCR) in the effector phase of acute bone marrow graft rejection. TCR V beta 5 transgenic mice lack effector cells able to cause graft rejection. , 1992, Journal of immunology.

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

[75]  S. Perlman,et al.  Selection of CTL escape mutants in mice infected with a neurotropic coronavirus: quantitative estimate of TCR diversity in the infected central nervous system. , 1999, Journal of immunology.

[76]  Scott N. Mueller,et al.  The Early Expression of Glycoprotein B from Herpes Simplex Virus Can Be Detected by Antigen-Specific CD8+ T Cells , 2003, Journal of Virology.

[77]  A. Lanzavecchia,et al.  Migration and Function of Antigen-Primed Nonpolarized T Lymphocytes in Vivo , 2001, The Journal of experimental medicine.

[78]  P. Marrack,et al.  The Repertoire of T Cells Shaped by a Single MHC/Peptide Ligand , 1996, Cell.

[79]  A. Lanzavecchia,et al.  Expression of two T cell receptor alpha chains: dual receptor T cells. , 1993, Science.

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

[81]  P. A. Peterson,et al.  Quantitation of peptide anchor residue contributions to class I major histocompatibility complex molecule binding. , 1993, The Journal of biological chemistry.

[82]  P. Fink,et al.  Positive selection of thymocytes. , 1995, Annual review of immunology.

[83]  F. Rieux-Laucat,et al.  Failure of HY-specific thymocytes to escape negative selection by receptor editing. , 2002, Immunity.

[84]  J. Whitton,et al.  Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR , 2001, Nature Immunology.

[85]  P. Klenerman,et al.  HIV: current opinion in escapology. , 2002, Current opinion in microbiology.

[86]  J. Altman,et al.  Individual variations in the murine T cell response to a specific peptide reflect variability in naive repertoires. , 1998, Immunity.

[87]  Rachael Keating,et al.  The Cytotoxic T-Cell Response to Herpes Simplex Virus Type 1 Infection of C57BL/6 Mice Is Almost Entirely Directed against a Single Immunodominant Determinant , 1999, Journal of Virology.

[88]  S. Turner,et al.  A dominant V beta bias in the CTL response after HSV-1 infection is determined by peptide residues predicted to also interact with the TCR beta-chain CDR3. , 1998, Molecular immunology.

[89]  D. Fremont,et al.  T cell receptor (TCR) recognition of MHC class I variants: intermolecular second-site reversion provides evidence for peptide/MHC conformational variation , 1996, The Journal of experimental medicine.

[90]  H. Gudmundsdottir,et al.  Dynamics and requirements of T cell clonal expansion in vivo at the single-cell level: effector function is linked to proliferative capacity. , 1999, Journal of immunology.

[91]  A. Lanzavecchia,et al.  Dual Receptor T‐Cells , 1995, Annals of the New York Academy of Sciences.

[92]  David M. Kranz,et al.  TCRs with high affinity for foreign pMHC show self-reactivity , 2003, Nature Immunology.

[93]  P. Anton van der Merwe,et al.  CDR3 loop flexibility contributes to the degeneracy of TCR recognition , 2003, Nature Immunology.

[94]  P. Marrack,et al.  T cell tolerance by clonal elimination in the thymus , 1987, Cell.

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

[96]  M. Oldstone,et al.  Defining parameters for successful immunocytotherapy of persistent viral infection. , 2000, Virology.

[97]  H. von Boehmer Shaping the T cell repertoire. , 2006, The Journal of Immunology.

[98]  P. Doherty,et al.  Quantitative analysis of the CD8+ T-cell response to readily eliminated and persistent viruses. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[99]  Alessandro Sette,et al.  Conserved T Cell Receptor Repertoire in Primary and Memory CD8 T Cell Responses to an Acute Viral Infection , 1998, The Journal of experimental medicine.