Functional management of an antiviral cytotoxic T-cell response

Lymphocytic choriomeningitis virus (LCMV) is known to induce strong, polyclonal cytotoxic T-lymphocyte (CTL) responses. Using a set of variant peptides derived from the major CTL epitope of LCMV, we analyzed the functional fine specificity of the LCMV-specific CTL response. During the primary response, almost all the tested peptides were recognized. In contrast, the secondary response was purged of all minor cross-reactivities and very few peptides were significantly recognized. This study is the first demonstration of the functional maturation of a T-cell response and has important clinical and biological implications.

[1]  K. Rajewsky Evolutionary and Somatic Immunological Memory , 1989 .

[2]  L. Staudt,et al.  V region gene usage and somatic mutation in the primary and secondary responses to influenza virus hemagglutinin. , 1990, Journal of immunology.

[3]  D. Hafler,et al.  Clonal expansion and persistence of human T cells specific for an immunodominant myelin basic protein peptide. , 1994, Journal of immunology.

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

[5]  H. Hengartner,et al.  Preferential usage of Vα4 and Vβ10 T cell receptor genes by lymphocytic choriomeningitis virus glycoprotein‐specific H‐2Db‐restricted cytotoxic T cells , 1990 .

[6]  L. Sherman,et al.  Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8. , 1992, Science.

[7]  H. Pircher,et al.  Tolerance induction by clonal deletion of CD4+8+ thymocytes in vitro does not require dedicated antigen‐presenting cells , 1993, European Journal of Immunology.

[8]  A. Sette,et al.  Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells , 1994, Nature.

[9]  Charles R. M. Bangham,et al.  Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition , 1991, Nature.

[10]  J. Mayer,et al.  Mature T cell reactivity altered by peptide agonist that induces positive selection , 1996, The Journal of experimental medicine.

[11]  D. Speiser,et al.  Viral peptide specific cytotoxic T lymphocytes are of high avidity to host-MHC but only low avidity to donor-MHC after allogeneic bone marrow transplantation. , 1995, Transplant immunology.

[12]  N. Hollander Effects of Anti‐Lyt Antibodies on T‐Cell Functions * , 1982, Immunological reviews.

[13]  Peter C. Doherty,et al.  Virus-specific CD8+ T-cell memory determined by clonal burst size , 1994, Nature.

[14]  M. Shenoy,et al.  TCR gene usage in experimental autoimmune myasthenia gravis pathogenesis. Usage of multiple TCRBV genes in the H-2b strains. , 1995, Journal of immunology.

[15]  D. Kioussis,et al.  The level of CD8 expression can determine the outcome of thymic selection , 1992, Cell.

[16]  Gregory F. Wu,et al.  Cytotoxic T cell-resistant variants are selected in a virus-induced demyelinating disease. , 1996, Immunity.

[17]  G. Kelsoe,et al.  Alternative pathways for the selection of antigen-specific peripheral T cells , 1996, Nature.

[18]  C V Jongeneel,et al.  Single-cell PCR analysis of TCR repertoires selected by antigen in vivo: a high magnitude CD8 response is comprised of very few clones. , 1996, Immunity.

[19]  Rolf M. Zinkernagel,et al.  Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo , 1990, Nature.

[20]  T. Mak,et al.  T cell responses are governed by avidity and costimulatory thresholds , 1996 .

[21]  V. Stewart,et al.  RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement , 1992, Cell.

[22]  Sarah Rowland-Jones,et al.  Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag variants , 1994, Nature.

[23]  R M Zinkernagel,et al.  Impairment and delay of neutralizing antiviral antibody responses by virus-specific cytotoxic T cells. , 1993, Journal of immunology.

[24]  M. Oldstone,et al.  Restricted V-segment usage in T-cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus , 1990, Journal of virology.

[25]  P. Klenerman,et al.  Cytotoxic T Lymphocyte Lysis Inhibited by Viable HIV Mutants , 1995, Science.

[26]  J. Banchereau,et al.  Generation of memory B cells and plasma cells in vitro , 1995, Science.

[27]  M. Buchmeier,et al.  The virology and immunobiology of lymphocytic choriomeningitis virus infection. , 1980, Advances in immunology.

[28]  R. Ahmed,et al.  Cytotoxic T-cell memory without antigen , 1994, Nature.

[29]  H. Pircher,et al.  Involvement of both T cell receptor Vα and Vβ variable region domains and α chain junctional region in viral antigen recognition , 1991 .

[30]  J. Gorski,et al.  Molecular analysis of T cell repertoires. Spectratypes generated by multiplex polymerase chain reaction and evaluated by radioactivity or fluorescence. , 1995, Human immunology.

[31]  Vincent K. Tsiagbe,et al.  The Path of Memory B‐Cell Development , 1992, Immunological reviews.

[32]  P. Fink,et al.  Identification of conserved T cell receptor CDR3 residues contacting known exposed peptide side chains from a major histocompatibility complex class I‐bound determinant , 1993, European journal of immunology.

[33]  H. Pircher,et al.  Characterization of virus‐specific cytotoxic T cell clones from allogeneic bone marrow chimeras , 1987, European journal of immunology.

[34]  T. Mak,et al.  T cell responses are governed by avidity and co‐stimulatory thresholds , 1996, European journal of immunology.

[35]  G. Nossal,et al.  Antigen-driven B cell differentiation in vivo , 1993, The Journal of experimental medicine.

[36]  H. Pircher,et al.  Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen , 1989, Nature.

[37]  M. Davis,et al.  Antigen-specific development of primary and memory T cells in vivo. , 1995, Science.

[38]  H. Pircher,et al.  Involvement of both T cell receptor V alpha and V beta variable region domains and alpha chain junctional region in viral antigen recognition. , 1991, European journal of immunology.