T Cell Receptor Recognition via Cooperative Conformational Plasticity

Gagnon, Susan J.; Borbulevych, O.Y.; Davis-Harrison, Rebecca L.; Turner, Richard V.; Damirjian, Marale; Wojnarowicz, Alison; Biddison, William E.; Baker, Brian M.

doi:10.1016/j.jmb.2006.08.045

Cited by 65 publications

(86 citation statements)

References 71 publications

(82 reference statements)

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“…Some kinetic studies are consistent with an induced fit process (101, 102), but others question it (95). TCR-pMHC interface complementarity may also be affected by changes in epitope configuration (90,92,94,99). There is generally less complementarity at the TCR-pMHC interface than between AgAb interfaces, in keeping with the substantially lower affinities of TCR-pMHC than Ag interactions with affinity-matured Abs (although not lower than Ag binding to preaffinity-matured Abs).…”

Section: T-cell Specificitymentioning

confidence: 92%

Evolving concepts of specificity in immune reactions

Eisen

Chakraborty

2010

Proc. Natl. Acad. Sci. U.S.A.

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Our goal is to provide a perspective on current understanding of the origins of specificity in immune reactions, a topic that has intrigued scientists for over a century. A fundamental property of adaptive immune responses is the ability to discriminate among an immense variety of substances by means of antibodies (Abs) and Ab-like receptors on T lymphocytes [T-cell receptors (TCRs)], each able to bind a particular chemical structure [the antigen (Ag)] and not, or only weakly, similar alternatives. Evidence has long existed, however, and has grown, especially recently, that while exhibiting remarkable specificity, many individual Abs and TCRs can also bind a variety of very different ligands. How can Ag recognition by these receptors exercise the great specificity for which they are renowned and yet react with a variety of different ligands (degeneracy)? We critically consider the mechanistic bases for this specificity/degeneracy enigma and also compare and contrast Ag recognition by Abs and TCRs.T cells | peptide-MHC complexes | receptor-ligand interactions | antibody isomerism

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Section: T-cell Specificitymentioning

confidence: 92%

Evolving concepts of specificity in immune reactions

Eisen

Chakraborty

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…The 3D model of the icefish Vb domain (region 21-137, accession number: AM886056) was created according to the homology modelling strategy and using as templates the experimental human and murine structures of Vb complexed with HLA-A2 (PDB code: 2GJ6, chain E) (Gagnon et al 2006) and I-Ak proteins (PDB code: 1G6R, chain B) (Degano et al 2000), respectively. An accurate procedure already described in previous papers (Facchiano et al 2001;Scapigliati et al 2004;Randelli et al 2008) was used to search for the best amino acid sequences alignment, being the sequence identity percentages between the icefish Vb domain and the human and murine homologous templates close to 30% (i.e.…”

Section: D Modelling Of Vb Domain From Chionodraco Hamatusmentioning

confidence: 99%

Evolution of cell‐mediated immune defences: Cloning and structural characterisation of the T cell receptor beta chain from the icefishChionodraco hamatus(Perciformes: Channichthyidae)

Buonocore

Randelli

Scala

et al. 2009

Italian Journal of Zoology

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Studies on the immune defence system of Antarctic fishes are of interest to investigate the presence of evolutionary adaptations to low temperature seawater. In the present paper, primers designed to conserved regions of TR b were used for the homology cloning of the icefish Chionodraco hamatus TR b chain cDNA. The full-length cDNA consists of 1219 nucleotides that translates in a single reading frame to give a predicted 304-amino acid molecule. The sequence shows highest nucleotide and amino acid identity with the sea bream (Sparus aurata) TR b. A multiple alignment with other known TR b molecules evidenced the presence of conserved amino acid residues involved in structural and functional domains within most teleost species. Real-time PCR analysis was used to investigate TR b basal expression, which was maximal in the thymus, followed by gills and spleen. Finally, the 3D structure of the icefish TR b was predicted by homology modelling and compared to Sparus aurata, a Teleost living in more temperate environmental conditions. The comparison of these two models suggests that the icefish TR b may be more flexible, as a consequence of a less compact structure and a lower number of H-bonds.

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“…The mechanisms of cross-activity generally accepted include molecular mimicry (56) and conformation adjustments. Significant changes in TCR CDR3 loops can take place upon binding (57)(58)(59) and CDR3 can occupy different conformations depending upon which ligand is bound (60,61 mechanisms produced occur simul-taneously in the interface, not limited to molecular mimicry and CDR loop shifts (62). Recently, it has been reported that the cross-reactivity correlated with a shrinking, increasingly hydrophobic TCR-ligand interface (63), and a few conserved amino acids in CDR1 and CDR2 were involved in the engagement (63,64).…”

Section: Molecular Basis Of Mhc-i/tcr Interactionmentioning

confidence: 99%