Key Points
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Antigen-specific T-cell responses are often characterized by the preferred use of specific T-cell receptors (which is known as TCR bias).
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The bias in TCR usage can be categorized based on the diversity in a specific T-cell population.
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There is evidence that after infection, the selection of a diverse TCR repertoire correlates with increased levels of immune protection.
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Consistent selection by different individuals of the same antigen-specific TCR sequences is an example of a 'public' TCR repertoire. A 'private' TCR repertoire occurs when there is little or no overlap in TCR sequences between individuals.
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TCR bias can be influenced by many factors, such as thymic selection and antigen-driven selection, which can narrow the available T-cell repertoire over time.
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The topology of a given peptide–MHC complex is an important factor in determining the level of TCR bias in a responding T-cell population.
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The most extreme TCR bias (type 3) is associated with peptide–MHC complexes that present unique challenges for recognition.
Abstract
Antigen-specific T-cell responses induced by infection, transplantation, autoimmunity or hypersensitivity are characterized by cells expressing biased profiles of T-cell receptors (TCRs) that are selected from a diverse, naive repertoire. Here, we review the evidence for these TCR biases, focusing on crystallographic analysis of the structural constraints that determine the binding of a TCR to its ligand and the persistence of certain TCRs in an immune repertoire. We discuss the ways in which diversity in a selected TCR repertoire can contribute to protective immunity and the implications of this for vaccine design and immunotherapy.
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References
Davis, M. M. & Chien, Y. H. in Fundamental Immunology (ed. Paul, W. E.) 341–366 (Lippincott-Raven, Philadelphia, 1999).
Lefranc, M. P. et al. IMGT, the international ImMunoGeneTics database. Nucleic Acids Res. 27, 209–212 (1999).
Chothia, C., Boswell, D. R. & Lesk, A. M. The outline structure of the T-cell αβ receptor. EMBO J. 7, 3745–3755 (1988).
Pannetier, C. et al. The sizes of the CDR3 hypervariable regions of the murine T-cell receptor β-chains vary as a function of the recombined germ-line segments. Proc. Natl Acad. Sci. USA 90, 4319–4323 (1993).
Cabaniols, J. P ., Fazilleau, N., Casrouge, A., Kourilsky, P. & Kanellopoulos, J. M. Most αβ T cell receptor diversity is due to terminal deoxynucleotidyl transferase. J. Exp. Med. 194, 1385–1390 (2001).
Rock, E. P., Sibbald, P. R., Davis, M. M. & Chien, Y. H. CDR3 length in antigen-specific immune receptors. J. Exp. Med. 179, 323–328 (1994).
Garboczi, D. N. et al. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 384, 134–141 (1996).
Garcia, K. C. et al. An αβ T cell receptor structure at 2.5 Å and its orientation in the TCR–MHC complex. Science 274, 209–219 (1996).
Kjer-Nielsen, L. et al. A structural basis for the selection of dominant αβ T cell receptors in antiviral immunity. Immunity 18, 53–64 (2003).
Stewart-Jones, G. B., McMichael, A. J., Bell, J. I., Stuart, D. I. & Jones, E. Y. A structural basis for immunodominant human T cell receptor recognition. Nature Immunol. 4, 657–663 (2003). References 9 and 10 indicate that TCRs found in type 3 TCR bias have specific structural requirements for optimal recognition of their cognate peptide–MHC complexes.
Reinherz, E. L. et al. The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 286, 1913–1921 (1999).
Ding, Y. H., Baker, B. M., Garboczi, D. N., Biddison, W. E. & Wiley, D. C. Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical. Immunity 11, 45–56 (1999).
Tynan, F. E. et al. T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide. Nature Immunol. 6, 1114–1122 (2005).
Maynard, J. et al. Structure of an autoimmune T cell receptor complexed with class II peptide–MHC: insights into MHC bias and antigen specificity. Immunity 22, 81–92 (2005).
Degano, M. et al. A functional hot spot for antigen recognition in a superagonist TCR/MHC complex. Immunity 12, 251–261 (2000).
Reiser, J. B. et al. Crystal structure of a T cell receptor bound to an allogeneic MHC molecule. Nature Immunol. 1, 291–297 (2000).
Reiser, J. B. et al. A T cell receptor CDR3β loop undergoes conformational changes of unprecedented magnitude upon binding to a peptide/MHC class I complex. Immunity 16, 345–354 (2002).
Cibotti, R. et al. Public and private Vβ T cell receptor repertoires against hen egg white lysozyme (HEL) in nontransgenic versus HEL transgenic mice. J. Exp. Med. 180, 861–872 (1994).
Messaoudi, I., Guevara Patino, J. A., Dyall, R., LeMaoult, J. & Nikolich-Zugich, J. Direct link between MHC polymorphism, T cell avidity, and diversity in immune defense. Science 298, 1797–1800 (2002). References 19 and 21 show that a positive outcome after viral infection correlates with broad TCR-repertoire diversity.
Webb, A. I. et al. The structure of H-2Kb and Kbm8 complexed to a herpes simplex virus determinant: evidence for a conformational switch that governs T cell repertoire selection and viral resistance. J. Immunol. 173, 402–409 (2004).
Slifka, M. K. & Whitton, J. L. Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR. Nature Immunol. 2, 711–717 (2001).
Price, D. A. et al. T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. Immunity 21, 793–803 (2004).
Evans, D. T. et al. Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. Nature Med. 5, 1270–1276 (1999).
Barouch, D. H. et al. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes. Nature 415, 335–339 (2002).
Nikolich-Zugich, J., Slifka, M. K. & Messaoudi, I. The many important facets of T-cell repertoire diversity. Nature Rev. Immunol. 4, 123–132 (2004).
Acha-Orbea, H. et al. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 54, 263–273 (1988).
Aebischer, T., Oehen, S. & Hengartner, H. Preferential usage of Vα4 and Vβ10 T cell receptor genes by lymphocytic choriomeningitis virus glycoprotein-specific H2-Db-restricted cytotoxic T cells. Eur. J. Immunol. 20, 523–531 (1990).
Argaet, V. P. et al. Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein–Barr virus. J. Exp. Med. 180, 2335–2340 (1994).
Babbe, H. et al. Clonal expansions of CD8+ T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J. Exp. Med. 192, 393–404 (2000).
Casanova, J. L. et al. H2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity. J. Exp. Med. 176, 439–447 (1992).
Casanova, J. L., Romero, P., Widmann, C., Kourilsky, P. & Maryanski, J. L. 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. J. Exp. Med. 174, 1371–1383 (1991).
Cose, S. C., Kelly, J. M. & Carbone, F. R. Characterization of diverse primary herpes simplex virus type 1 gB-specific cytotoxic T-cell response showing a preferential Vβ bias. J. Virol. 69, 5849–5852 (1995).
Deckhut, A. M. et al. Prominent usage of Vβ8.3 T cells in the H2-Db-restricted response to an influenza A virus nucleoprotein epitope. J. Immunol. 151, 2658–2666 (1993).
Fasso, M. et al. T cell receptor (TCR)-mediated repertoire selection and loss of TCR Vβ diversity during the initiation of a CD4+T cell response in vivo. J. Exp. Med. 192, 1719–1730 (2000).
Callan, M. F. et al. Large clonal expansions of CD8+ T cells in acute infectious mononucleosis. Nature Med. 2, 906–911 (1996).
Godthelp, B. C., van Tol, M. J., Vossen, J. M. & van den Elsen, P. J. Longitudinal analysis of T cells responding to tetanus toxoid in healthy subjects as well as in pediatric patients after bone marrow transplantation: the identification of identical TCR-CDR3 regions in time suggests long-term stability of at least part of the antigen-specific TCR repertoire. Int. Immunol. 13, 507–518 (2001).
Kelly, J. M. 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. Eur. J. Immunol. 23, 3318–3326 (1993).
Kedzierska, K., Turner, S. J. & Doherty, P. C. Conserved T cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope. Proc. Natl Acad. Sci. USA 101, 4942–4947 (2004).
Belz, G. T., Stevenson, P. G. & Doherty, P. C. Contemporary analysis of MHC-related immunodominance hierarchies in the CD8+ T cell response to influenza A viruses. J. Immunol. 165, 2404–2409 (2000).
McHeyzer-Williams, M. G. & Davis, M. M. Antigen-specific development of primary and memory T cells in vivo. Science 268, 106–111 (1995).
Oksenberg, J. R. et al. Selection for T-cell receptor Vβ-Dβ-Jβ gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature 362, 68–70 (1993).
Pantaleo, G. et al. Major expansion of CD8+ T cells with a predominant Vβ usage during the primary immune response to HIV. Nature 370, 463–467 (1994).
Pewe, L. & Perlman, S. Immune response to the immunodominant epitope of mouse hepatitis virus is polyclonal, but functionally monospecific in C57Bl/6 mice. Virology 255, 106–116 (1999).
Price, D. A. et al. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J. Exp. Med. 202, 1349–1361 (2005). This study shows that co-receptor activity might help to ensure diversification of the responding TCR repertoire.
Turner, S. J. & Carbone, F. R. A dominant Vβ bias in the CTL response after HSV-1 infection is determined by peptide residues predicted to also interact with the TCR β-chain CDR3. Mol. Immunol. 35, 307–316 (1998).
Moss, P. A. et al. Extensive conservation of α- and β-chains of the human T-cell antigen receptor recognizing HLA-A2 and influenza A matrix peptide. Proc. Natl Acad. Sci. USA 88, 8987–8990 (1991).
Lehner, P. J. et al. Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the Vβ17 gene segment. J. Exp. Med. 181, 79–91 (1995).
Callan, M. F. et al. T cell selection during the evolution of CD8+ T cell memory in vivo. Eur. J. Immunol. 28, 4382–4390 (1998).
Baker, F. J., Lee, M., Chien, Y. H. & Davis, M. M. Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice. Proc. Natl Acad. Sci. USA 99, 9374–9379 (2002).
Torres-Nagel, N., Deutschlander, A., Herrmann, T., Arden, B. & Hunig, T. Control of TCR Vα-mediated positive repertoire selection and alloreactivity by differential Jα usage and CDR3α composition. Int. Immunol. 9, 1441–1452 (1997).
Wilson, J. D. et al. Oligoclonal expansions of CD8+ T cells in chronic HIV infection are antigen specific. J. Exp. Med. 188, 785–790 (1998).
Wills, M. R. et al. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp65: frequency, specificity, and T-cell receptor usage of pp65-specific CTL. J. Virol. 70, 7569–7579 (1996).
Trautmann, L. et al. Selection of T cell clones expressing high-affinity public TCRs within human cytomegalovirus-specific CD8 T cell responses. J. Immunol. 175, 6123–6132 (2005). References 26–53 provide examples of different types of TCR bias in a range of immune conditions and models.
Bousso, P. et al. Individual variations in the murine T cell response to a specific peptide reflect variability in naive repertoires. Immunity 9, 169–178 (1998).
Casrouge, A. et al. Size estimate of the αβ TCR repertoire of naive mouse splenocytes. J. Immunol. 164, 5782–5787 (2000).
Arstila, T. P. et al. A direct estimate of the human αβ T cell receptor diversity. Science 286, 958–961 (1999). References 55 and 56 provide mathematical estimates of the naive mouse and human T-cell repertoires, respectively.
Correia-Neves, M., Waltzinger, C., Mathis, D. & Benoist, C. The shaping of the T cell repertoire. Immunity 14, 21–32 (2001). This study shows that positive selection of particular TCR V regions can result in bias in the naive T-cell repertoire.
Teng, M. K. et al. Identification of a common docking topology with substantial variation among different TCR–peptide–MHC complexes. Curr. Biol. 8, 409–412 (1998).
Huseby, E. S. et al. How the T cell repertoire becomes peptide and MHC specific. Cell 122, 247–260 (2005).
Sim, B. C., Zerva, L., Greene, M. I. & Gascoigne, N. R. Control of MHC restriction by TCR Vα CDR1 and CDR2. Science 273, 963–966 (1996).
Sim, B. C., Lo, D. & Gascoigne, N. R. Preferential expression of TCR Vα regions in CD4/CD8 subsets: class discrimination or co-receptor recognition? Immunol. Today 19, 276–282 (1998).
Saito, H. et al. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature 309, 757–762 (1984).
Borg, N. A. et al. The CDR3 regions of an immunodominant T cell receptor dictate the 'energetic landscape' of peptide–MHC recognition. Nature Immunol. 6, 171–180 (2005).
Ely, L. K. et al. Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction. Proc. Natl Acad. Sci. USA 103, 6641–6646 (2006).
Gett, A. V., Sallusto, F., Lanzavecchia, A. & Geginat, J. T cell fitness determined by signal strength. Nature Immunol. 4, 355–360 (2003).
Kaech, S. M. & Ahmed, R. Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naive cells. Nature Immunol. 2, 415–422 (2001).
Malherbe, L., Hausl, C., Teyton, L. & McHeyzer-Williams, M. G. Clonal selection of helper T cells is determined by an affinity threshold with no further skewing of TCR binding properties. Immunity 21, 669–679 (2004). This paper shows that TCRs expressing a specific CDR motif can be selected from the naive T-cell pool into the responding T-cell population.
Kedzierska, K., La Gruta, N. L., Davenport, M. P., Turner, S. J. & Doherty, P. C. Contribution of T cell receptor affinity to overall avidity for virus-specific CD8+ T cell responses. Proc. Natl Acad. Sci. USA 102, 11432–11437 (2005).
Wooldridge, L. et al. Interaction between the CD8 coreceptor and major histocompatibility complex class I stabilizes T cell receptor–antigen complexes at the cell surface. J. Biol. Chem. 280, 27491–27501 (2005).
Malherbe, L. et al. Selective activation and expansion of high-affinity CD4+ T cells in resistant mice upon infection with Leishmania major. Immunity 13, 771–782 (2000).
McHeyzer-Williams, L. J., Panus, J. F., Mikszta, J. A. & McHeyzer-Williams, M. G. Evolution of antigen-specific T cell receptors in vivo: preimmune and antigen-driven selection of preferred complementarity-determining region 3 (CDR3) motifs. J. Exp. Med. 189, 1823–1838 (1999).
Busch, D. H. & Pamer, E. G. T cell affinity maturation by selective expansion during infection. J. Exp. Med. 189, 701–710 (1999).
Zhong, W. & Reinherz, E. L. In vivo selection of a TCR Vβ repertoire directed against an immunodominant influenza virus CTL epitope. Int. Immunol. 16, 1549–1559 (2004).
Sourdive, D. J. et al. Conserved T cell receptor repertoire in primary and memory CD8 T cell responses to an acute viral infection. J. Exp. Med. 188, 71–82 (1998).
Turner, S. J., Diaz, G., Cross, R. & Doherty, P. C. Analysis of clonotype distribution and persistence for an influenza virus-specific CD8+ T cell response. Immunity 18, 549–559 (2003).
Maryanski, J. L., Jongeneel, C. V., Bucher, P., Casanova, J. L. & Walker, P. R. Single-cell PCR analysis of TCR repertoires selected by antigen in vivo: a high magnitude CD8 response is comprised of very few clones. Immunity 4, 47–55 (1996).
Lin, M. Y. & Welsh, R. M. Stability and diversity of T cell receptor repertoire usage during lymphocytic choriomeningitis virus infection of mice. J. Exp. Med. 188, 1993–2005 (1998). References 74–77 show that the TCR repertoire that is selected during the acute phase of an immune response is stable into memory and subsequent recall responses.
Chen, Z. W. et al. The TCR repertoire of an immunodominant CD8+ T lymphocyte population. J. Immunol. 166, 4525–4533 (2001).
Pantaleo, G. et al. Evidence for rapid disappearance of initially expanded HIV-specific CD8+ T cell clones during primary HIV infection. Proc. Natl Acad. Sci. USA 94, 9848–9853 (1997).
Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R. & Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol. 77, 4911–4927 (2003).
Wallace, M. E. et al. Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1. Immunity 12, 547–556 (2000). This study shows that deletion of a specific TCR gene segment results in a lack of T cells capable of responding to viral infection.
Man, S., Ridge, J. P. & Engelhard, V. H. Diversity and dominance among TCR recognizing HLA-A2.1+ influenza matrix peptide in human MHC class I transgenic mice. J. Immunol. 153, 4458–4467 (1994).
Fazilleau, N. et al. Vα and Vβ public repertoires are highly conserved in terminal deoxynucleotidyl transferase-deficient mice. J. Immunol. 174, 345–355 (2005).
Burrows, S. R., Khanna, R., Burrows, J. M. & Moss, D. J. An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross-reactive with a single Epstein–Barr virus CTL epitope: implications for graft-versus-host disease. J. Exp. Med. 179, 1155–1161 (1994).
Burrows, S. R. et al. T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen. J. Exp. Med. 182, 1703–1715 (1995).
Burrows, S. R. et al. Cross-reactive memory T cells for Epstein–Barr virus augment the alloresponse to common human leukocyte antigens: degenerate recognition of major histocompatibility complex-bound peptide by T cells and its role in alloreactivity. Eur. J. Immunol. 27, 1726–1736 (1997).
Sun, Z. J., Kim, K. S., Wagner, G. & Reinherz, E. L. Mechanisms contributing to T cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3εγ heterodimer. Cell 105, 913–923 (2001).
Maryanski, J. L. et al. The diversity of antigen-specific TCR repertoires reflects the relative complexity of epitopes recognized. Hum. Immunol. 54, 117–128 (1997).
La Gruta, N. L. et al. A virus-specific CD8+ T cell immunodominance hierarchy determined by antigen dose and precursor frequencies. Proc. Natl Acad. Sci. USA 103, 994–999 (2006).
Turner, S. J. et al. Lack of prominent peptide–major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations. Nature Immunol. 6, 382–389 (2005). This study shows a direct correlation between the structural features of a peptide–MHC complex and TCR-repertoire diversity of the responding T-cell population.
Townsend, A. R. et al. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44, 959–968 (1986).
Belz, G. T., Xie, W., Altman, J. D. & Doherty, P. C. A previously unrecognized H2-Db-restricted peptide prominent in the primary influenza A virus-specific CD8+ T-cell response is much less apparent following secondary challenge. J. Virol. 74, 3486–3493 (2000).
Meijers, R. et al. Crystal structures of murine MHC Class I H2-Db and Kb molecules in complex with CTL epitopes from influenza A virus: implications for TCR repertoire selection and immunodominance. J. Mol. Biol. 345, 1099–1110 (2005).
Hoffmann, E., Krauss, S., Perez, D., Webby, R. & Webster, R. G. Eight-plasmid system for rapid generation of influenza virus vaccines. Vaccine 20, 3165–3170 (2002).
Tynan, F. E. et al. The high resolution structures of highly bulged viral epitopes bound to the major histocompatability class I: implications for T-cell receptor engagement and T-cell immunodominance. J. Biol. Chem. 280, 23900–23909 (2005).
Altman, J. D. et al. Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94–96 (1996).
Acknowledgements
We thank N. La Gruta, K. Kedzierska, S. Burrows and S. Perlman for critical review of the manuscript. Support was provided by a Burnet Fellowship of the National Health and Medical Research Council (NHMRC) of Australia (P.C.D.), an NHMRC R.D. Wright Fellowship (S.J.T.) and an Australian Research Council (ARC) Professorial and Federation Fellowship (J.R.). Further funding came from the Government of Victoria (Australia), the ARC, the NHMRC, the Juvenile Diabetes Research Foundation, a United States Public Health Service grant and the American Lebanese Syrian Associated Charities at St Jude Children's Research Hospital (Memphis, Tennessee, USA).
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Glossary
- Positive selection
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The process in the thymus that selects thymocytes expressing T-cell receptors (TCRs) that can interact weakly with self-MHC molecules. This weak interaction generates differentiation and survival signals in these lymphocytes, the TCRs of which later recognize foreign peptides bound to self-MHC. Positive selection establishes the MHC-restricted T-cell repertoire.
- Negative selection
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The deletion of self-reactive thymocytes in the thymus. Thymocytes expressing T-cell receptors that strongly recognize self-peptide bound to self-MHC molecules undergo apoptosis in response to the signalling generated by high-affinity binding.
- TCR bias
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The selection of antigen-specific T cells that show preferential usage of particular T-cell receptor (TCR) variable region gene-segment combinations in response to antigen. TCR bias can be grouped into type 1, type 2 or type 3 TCR bias.
- T-cell fitness
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The ability of a given naive T-cell precursor to cross a threshold of TCR-mediated signals that enable selection into the antigen-specific immune repertoire.
- Best-fit TCR
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A T-cell receptor (TCR) that shows marked structural complementarity with its cognate peptide–MHC antigen, resulting in optimal, high-avidity interactions. Conversely, a less-fit TCR does not show good structural complementarity with cognate peptide–MHC complexes, resulting in suboptimal, low-avidity interactions.
- Peptide–MHC tetramer
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Biotinylated monomeric MHC molecules are folded with a specific peptide in the binding groove and tetramerized with a fluorescently labelled streptavidin molecule. Tetramers will bind to T cells that express T-cell receptors specific for the cognate peptide.
- Reverse genetics
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Genetic analysis that proceeds from genotype to phenotype through gene-manipulation techniques. For example, a reverse-genetics strategy enables the generation of infectious influenza A viruses from cloned plasmid cDNAs. The plasmid-based system enables mutations to be introduced into the coding regions of specific virus gene segments using recombinant PCR.
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Turner, S., Doherty, P., McCluskey, J. et al. Structural determinants of T-cell receptor bias in immunity. Nat Rev Immunol 6, 883–894 (2006). https://doi.org/10.1038/nri1977
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