Analysis of tetanus toxin peptide/DR recognition by human T cell receptors reconstituted into a murine T cell hybridoma

We have previously reported that human T cell receptors (TcR) selected in the class II‐restricted (HLA‐DRB1*1302) response to a tetanus toxin peptide (tt830‐843) frequently used the Vβ2 germ‐line segment which paired with several Vα segments and that the putative CDR3 of both α and β chains showed remarkable heterogeneity. To analyze the structural basis for recognition of the tt830‐843/DR complex, five of these TcR were reconstituted into a murine T cell hybridoma, 58 α−β−, by expressing the human α and β variable regions joined to the mouse α and β constant regions, respectively. The chimeric TcR, expressing the same Vβ germ‐line segment (Vβ2), two expressing Vα21.1, twoVα17.1 and one Vα8.1 were shown to have the expected antigen specificity and DR restriction.

[1]  D. Wiley,et al.  Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1 , 1993, Nature.

[2]  R. Saiki,et al.  A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. , 1988, Nucleic acids research.

[3]  J. Claverie,et al.  Implications of a Fab-like structure for the T-cell receptor. , 1989, Immunology today.

[4]  A. Rao,et al.  Functional analysis of the antigen binding site on the T cell receptor alpha chain , 1992, The Journal of experimental medicine.

[5]  H. Mcdevitt,et al.  Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention , 1988, Cell.

[6]  Ursula Esser,et al.  Mapping T-cell receptor–peptide contacts by variant peptide immunization of single-chain transgenics , 1992, Nature.

[7]  U. Landegren Measurement of cell numbers by means of the endogenous enzyme hexosaminidase. Applications to detection of lymphokines and cell surface antigens. , 1984, Journal of immunological methods.

[8]  B. Malissen,et al.  Derivation of a T cell hybridoma variant deprived of functional T cell receptor α and β chain transcripts reveals a nonfunctional α‐mRNA of BW5147 origin , 1989, European journal of immunology.

[9]  A Sette,et al.  Truncation analysis of several DR binding epitopes. , 1991, Journal of immunology.

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

[11]  J. Casanova,et al.  T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire , 1991, The Journal of experimental medicine.

[12]  E. Rock,et al.  Transfer of putative complementarity-determining region loops of T cell receptor V domains confers toxin reactivity but not peptide/MHC specificity. , 1993, Journal of Immunology.

[13]  C. Janeway,et al.  An MHC interaction site maps to the amino-terminal half of the T cell receptor α chain variable domain , 1992, Cell.

[14]  P. Fink,et al.  T cell receptor junctional regions and the MHC molecule affect the recognition of antigenic peptides by T cell clones. , 1990, Journal of immunology.

[15]  Don C. Wiley,et al.  Atomic structure of a human MHC molecule presenting an influenza virus peptide , 1992, Nature.

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

[17]  P. Colman,et al.  Structure of antibody-antigen complexes: implications for immune recognition. , 1988, Advances in immunology.

[18]  A. Lanzavecchia,et al.  Preferential V beta gene usage and lack of junctional sequence conservation among human T cell receptors specific for a tetanus toxin- derived peptide: evidence for a dominant role of a germline-encoded V region in antigen/major histocompatibility complex recognition , 1992, The Journal of experimental medicine.

[19]  J. Bodmer,et al.  HLA-DR and -DQ epitopes and monoclonal antibody specificity. , 1989, Immunology today.

[20]  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 .

[21]  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.

[22]  N. Shastri,et al.  Requirement for association of p56 lck with CD4 in antigen-specific signal transduction in T cells , 1991, Cell.

[23]  A. Levinson,et al.  Isolation and expression of an altered mouse dihydrofolate reductase cDNA. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[24]  J. Wither,et al.  Amino acid residues in the T cell receptor CDR3 determine the antigenic reactivity patterns of insulin-reactive hybridomas. , 1991, Journal of immunology.

[25]  R. Karr,et al.  The role of polymorphic HLA-DR beta chain residues in presentation of viral antigens to T cells , 1990, The Journal of experimental medicine.

[26]  P. Parham,et al.  Position 71 in the α helix of the DRβ domain is predicted to influence peptide binding and plays a central role in allorecognition , 1993 .

[27]  A. Taylor,et al.  Structure-function relationships among highly diverse T cells that recognize a determinant from influenza virus hemagglutinin , 1990, The Journal of experimental medicine.

[28]  J. Rothbard,et al.  Interactions between Immunogenic Peptides and MHC Proteins , 1991 .

[29]  A. Horwich,et al.  Expression of amplified DNA sequences for ornithine transcarbamylase in HeLa cells: arginine residues may be required for mitochondrial import of enzyme precursor , 1985, The Journal of cell biology.

[30]  J. Casanova,et al.  H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity , 1992, The Journal of experimental medicine.

[31]  A. Lesk,et al.  The outline structure of the T‐cell alpha beta receptor. , 1988, The EMBO journal.

[32]  P. Fink,et al.  Selection of amino acid sequences in the beta chain of the T cell antigen receptor. , 1988, Science.

[33]  S. Hedrick,et al.  Site-directed mutations in the VDJ junctional region of a T cell receptor β chain cause changes in antigenic peptide recognition , 1988, Cell.

[34]  J. Casanova,et al.  T cell receptor selection by and recognition of two class I major histocompatibility complex-restricted antigenic peptides that differ at a single position , 1993, The Journal of experimental medicine.

[35]  P. Marrack,et al.  Selective expansion of T cells expressing V beta 2 in toxic shock syndrome , 1990, The Journal of experimental medicine.

[36]  J. Danska,et al.  The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides , 1990, The Journal of experimental medicine.

[37]  J. Sidney,et al.  Single amino acid changes in DR and antigen define residues critical for peptide-MHC binding and T cell recognition. , 1991, Journal of immunology.

[38]  M. Gefter,et al.  Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition. , 1990, Journal of immunology.

[39]  P. A. Peterson,et al.  Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. , 1994, Science.

[40]  J. Bluestone,et al.  Identification of a monoclonal antibody specific for a murine T3 polypeptide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[41]  N. Varin‐Blank,et al.  Expression of the alpha chain of human Fc epsilon RI in transfected rat basophilic leukemia cells: functional activation after sensitization with human mite-specific IgE. , 1993, International archives of allergy and immunology.

[42]  P. Gregersen,et al.  Analysis of the molecular specificities of anti-class II monoclonal antibodies by using L cell transfectants expressing HLA class II molecules. , 1988, Journal of immunology.

[43]  D. Wiley,et al.  A hypothetical model of the foreign antigen binding site of Class II histocompatibility molecules , 1988, Nature.

[44]  J. Lippincott-Schwartz,et al.  Failure to synthesize the T Cell CD3-ζ chain: Structure and function of a partial T cell receptor complex , 1988, Cell.

[45]  M. A. Saper,et al.  Structure of the human class I histocompatibility antigen, HLA-A2 , 1987, Nature.

[46]  P. Marrack,et al.  Antigen recognition properties of mutant V beta 3+ T cell receptors are consistent with an immunoglobulin-like structure for the receptor , 1993, The Journal of experimental medicine.