Abstract
The kinetics of the interaction between T cell receptor (TCR) and major histocompatibility complex (MHC) has an important role in determining thymocyte-positive and-negative selection in the thymus, as well as in T cell activation. The α chain of the TCR is the major player in determining how the TCR fits onto the MHC ligand, and thus has a major role in determining whether a T cell develops as class I or class II restricted. In this article, we summarize recent data from our laboratory and otherson the role of poly-morphism in the Vα combining site in determining MHC class restriction, and on kinetic parameters in thymocyte selection.
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References
Garcia KC, Teyton L, Wilson JA: Structural basis of T cell recognition. Annu Rev Immunol 1999;17: 369–397.
Kersh GJ, Allen PM: Essential flexibility in the T-cell recognition of antigen. Nature 1996;380:495–498.
Goldrath AW, Bevan MJ: Selecting and maintaining a diverse T-cell repertoire. Nature 1999;402: 255–262.
Sim B-C, Lo D, Gascoigne NRJ: Preferential expression of TCR V α, regions in CD4/CD8 subsets: class discrimination or co-receptor recognition? Immunol Today 1998;19:276–282.
Sim B-C, Gascoigne NRJ: Reciprocal expression in CD4 or CD8 subsets of different members of the Vα11 genefamily correlates with sequence polymorphism. J Immunol 1999;162:3153–3159.
Correia-Neves M, Waltzinger C, Wurtz J-M, Benoist C, Mathis D: Amino acids specifiying MHC class preference in TCR Vα2 regions. J Immunol 1999;163: 5471–5477.
Sim B-C, Zerva L, Greene MI, Gascoigne NRJ: Control of MHC restriction by TCR Vα CDR1 and CDR2. Science 1996;273: 963–966.
Sim B-C, Wung JL, Gascoigne NRJ: Poly morphism within a TCRAV family influences the repertoire through class 1/11 restriction. J Immunol 1998;160: 1204–1211.
Alam SM, Travers PJ, Wung JL, Nasholds W, Redpath S, Jameson SC, Gascoigne NRJ: T cell receptor affinity and thymocyte positive selection. Nature 1996;381: 616–620.
Manning TC, Parke EA, Teyton L, Kranz DM: Effects of complementarity determining region mutations on the affinity of an α/β T cell receptor: measuring the energy associated with CD4/CD8 repertoire skewing. J Exp Med 1999;189:461–470.
Mateckak EO, Killeen N, Hedrick SM, Fowlkes BJ: MHC class II-specific T cells can develop in the CD8 lineage when CD4 is absent. Immunity 1996;4:337–347.
Reinherz EL, Tan K, Tang L, Kern P, Liu J, Xiong Y, Hussey RE, Smolyar A, Hare B, Zhang R, Joachimiak A, Chang H-C, Wagner G, Wang J: The crystal structure of a T cell receptor in complex with peptide and MHC class II. Science 1999;286:1913–1921.
Wilson IA: Class-conscious TCR? Science 1999;286:1867–1868.
Manning TC, Schlueter CJ, Brodnicki TC, Parke EA, Speir JA, Garcia KC, Teyton L, Wilson IA, Kranz DM:Alanine scanning mutagenesis of an αβ T cell receptor: mapping the energy of antigen recognition. Immunity 1998;8: 413–425.
Garcia KC, Degano M, Pease LR, Huang M, Peterson PA, Tayton L, Wilson A: Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen. Science 1998;279:1166–1172.
Sim B-C, Aftahi N, Reilly C, Bogen B, Schwartz RH, Gascoigne NRJ, Lo D: Thymicskewing of the CD4/CD8 ratio maps with the T cell receptor α-chain locus. Curr Biol 1998;8:701–704.
Janeson SC, Hogquist KA, Bevan MJ: Positive selection of thymocytes. Annu Rev Immunol 1995; 13:93–126.
Sebzda E, Mariathasan S, Ohteki T, Jones R, Bachmann MF, Ohashi PS: Selection of the T cell repertoire. Annu Rev Immunol 1999;17: 829–874.
Matsui K, Boniface JJ, Steffner P, Reay PA, Davis MM: Kinetics of T-cell receptor bindign to peptide/l-Ek complexes: correlation of the dissociation rate with T-cell responsiveness. Proc Natl Acad Sci USA 1994;91:12,862–12,866.
Lyors DS, Lieberman SA, Hampl J, Boniface JJ, Chien Y, Berg LJ, Davis MM: A TCR binds to antagonist ligands with lower affinities and faster dissociation rates than to agonists. Immunity 1996;5: 53–61.
Kersh GJ, Kersh EN, Fremont DH, Allen PM: High-and low-potency ligands with similar affinities for the TCR: the importance of kinetics in TCR signaling. Immunity 1998;9:817–826.
Alam SM, Davies GM, Lin CM, Zal T, Nasholds W, Jameson SC, Hogquist KA, Gascoigne NRJ, Travers PJ: Qualitative and quantitative differences in T cell receptor binding of agonist and antagonist ligands. Immunity 1999;10: 227–237.
Reich Z, Boniface JJ, Lyons DS, Borochov N, Wachtel EJ, Davis MM: Ligand-specific oligomerization of T-cell receptor molecules. Nature 1997;387:617–620.
Willcox BE, Gao GF, Wyer JR, Ladbury JE, Bell PA: TCR bindign to peptide-MHC stabilizes a flexible recognition interface. Immunity 1999;10:357–365.
Boniface JJ, Reich Z, Lyons DS, Davis MM: Thermodynamics of T cell receptor binding to peptid-MHC: evidence for a general mechanism of molecularscanning. Proc Natl Acad Sci USA 1999;96: 11,446–11,451.
Schlueter CJ, Manning TC, Schodin BA, Kranz DM: A residue in the center of peptide QL9 affects binding to both Ld and the T cell receptor. J Immunol 1996;157: 4478–4485.
Whelan JA, Dunbar PR, Price DA, Purbhoo MA, Lechner F, Ogg GS, Griffiths G, Phillips RE, Cerusdolo V, Swell AK: Specificity of CTL interactions with peptide-MHC class1 tetrameric complexes is temperature dependent. J Immunol 1999;163:4342–4348.
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Gascoigne, N.R.J., Alam, S.M., Lin, C.M. et al. T cell receptor binding kinetics and special role of Vα in T cell development and activation. Immunol Res 21, 225–231 (2000). https://doi.org/10.1385/IR:21:2-3:225
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DOI: https://doi.org/10.1385/IR:21:2-3:225