Amino Acids Specifying MHC Class Preference in TCR Vα2 Regions

Some TCR variable regions are preferentially expressed in CD4+ or CD8+ T cells, reflecting a predilection for interacting with MHC class II or class I molecules. The molecular basis for MHC class bias has been studied previously, in particular for Vα3 family members, pointing to a dominant role for two amino acid positions in complementary-determining regions (CDRs) 1 and 2. We have evaluated the generality of these findings by examining the MHC class bias of Vα2 family members, an attractive system because it shows more variability within the CDR1 and -2, exhibits variation in the framework regions, and includes a member for which the crystal structure has been determined. We find that preferential recognition of MHC class I or II molecules does not always depend on residues at the same positions of CDR1 and -2; rules for one family may be reversed in another. Instead, there are multiple influences exerted by various CDR1/2 positions as well as the CDR3s of both the TCR α- and TCR β-chains.

[1]  E. Padlan,et al.  The X-ray crystal structure of a Valpha2.6Jalpha38 mouse T cell receptor domain at 2.5 A resolution: alternate modes of dimerization and crystal packing. , 1999, Journal of molecular biology.

[2]  Gerhard Wagner,et al.  Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor , 1999, Nature Structural Biology.

[3]  David M. Kranz,et al.  Role of the T Cell Receptor α Chain in Stabilizing TCR-Superantigen-MHC Class II Complexes , 1999 .

[4]  N. Gascoigne,et al.  Reciprocal expression in CD4 or CD8 subsets of different members of the V alpha 11 gene family correlates with sequence polymorphism. , 1999, Journal of immunology.

[5]  C. Janeway,et al.  A molecular map of T cell development. , 1998, Immunity.

[6]  R. Schwartz,et al.  Thymic skewing of the CD4/CD8 ratio maps with the T-cell receptor α-chain locus , 1998, Current Biology.

[7]  D. Lo,et al.  Preferential expression of TCR V alpha regions in CD4/CD8 subsets: class discrimination or co-receptor recognition? , 1998, Immunology today.

[8]  D. Wiley,et al.  Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids. , 1998, Immunity.

[9]  A. Smolyar,et al.  Identification of a common docking topology with substantial variation among different TCR–peptide–MHC complexes , 1998, Current Biology.

[10]  N. Gascoigne,et al.  Polymorphism within a TCRAV family influences the repertoire through class I/II restriction. , 1998, Journal of immunology.

[11]  B. Arden.  Conserved motifs in T-cell receptor CDR1 and CDR2: implications for ligand and CD8 co-receptor binding. , 1998, Current opinion in immunology.

[12]  J. Fontecilla-Camps,et al.  The three‐dimensional structure of a T‐cell antigen receptor VαVβ heterodimer reveals a novel arrangement of the Vβ domain , 1997 .

[13]  Partho Ghosh,et al.  Structure of the complex between human T-cell receptor, viral peptide and HLA-A2 , 1996, Nature.

[14]  Robyn L. Stanfield,et al.  An αβ T Cell Receptor Structure at 2.5 Å and Its Orientation in the TCR-MHC Complex , 1996, Science.

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

[16]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[17]  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.

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

[19]  L. Hood,et al.  Organization, structure, and function of 95 kb of DNA spanning the murine T-cell receptor CαCδ region , 1992 .

[20]  S. Rastan,et al.  Lymphoid development in mice congenitally lacking T cell receptor alpha beta-expressing cells. , 1992, Science.

[21]  H. Pircher,et al.  Preferential positive selection of Vα2+CD8+ T cells in mouse strains expressing both H‐2k and T cell receptor Vαa haplotypes: determination with a Vα2‐specific monoclonal antibody , 1992, European journal of immunology.

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

[23]  K. Sharp,et al.  Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons , 1991, Proteins.

[24]  W. J. Esselman,et al.  T200 alternate exon use in murine lymphoid cells determined by reverse transcription-polymerase chain reaction. , 1989, Journal of immunology.

[25]  D. Loh,et al.  Tandem linkage and unusual RNA splicing of the T-cell receptor beta-chain variable-region genes. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[26]  R. Zinkernagel,et al.  The discovery of MHC restriction. , 1997, Immunology today.

[27]  V. Kouskoff,et al.  Cassette vectors directing expression of T cell receptor genes in transgenic mice. , 1995, Journal of immunological methods.