The Specificity and Orientation of a TCR to its Peptide–MHC Class II Ligands

Abstract

A T cell-mediated immune response is mainly determined by the 3-5 aa residues that protrude upwards from a peptide bound to an MHC molecule. Alterations of these peptide residues can diminish, eliminate or radically alter the signal that the T cell receives through its T cell receptor (TCR). We have used peptide immunizations of normal mice and mice carrying alpha or beta chain TCR transgenes to identify three distinct peptide contact points. One, near the carboxyl terminus of the peptide, involves the beta chain CDR3 region; the second was centrally located and interacted with both the alpha and beta chain CDR3 loops; the third was near the amino terminus of the peptide, and affected V alpha gene usage, but not the structure of CDR3 of either TCR chain. Based on these results, we propose an orientation for the TCR of this cloned line and argue for its generality.

Inhibition of altered peptide ligand‐mediated antagonism of human GAD65‐responsive CD4+ T cells by non‐antagonizable T cells

“…However, two of the APL were capable of antagonizing five out of the six hGAD65 (555-567)-responsive clones. These two APL have substitutions at the p5 position, a major contact site for TCR recognition of MHC-peptide [24][25][26]. The finding that no single APL was able to antagonize all six clones and that many were agonistic is similar to findings on MBP APL [27].…”

Impact of early expression of TCR α chain on thymocyte development

“…2B4 § -TG and 2B4 § -KI mice express the same TCR § chain with different regulatory elements [13,14], while 2B4 § -TG and D10 § -TG mice express different TCR § chains but use the same TCR transgenic expression vector [13,15]. All three mice express the transgenic § chain prematurely at the DN stage [13][14][15]. Analysis of their thymic cellularity and CD4/CD8 subset distribution showed that the total thymocyte numbers of the 2B4 § -KI, 2B4 § -TG, and D10 § -TG mice were less than˚20% that of B6 mice ( Fig.…”

Structural Analysis of TCRα and β Chains from Human T‐Cell Clones Specific for Small Nuclear Ribonucleoprotein Polypeptides Sm‐D, Sm‐B and U1–70 kDa: TCR Complementarity Determining Region 3 Usage Appears Highly Conserved

“…Each of these regions forms a loop that point away from the T cell and contacts the antigen-HLA complex [8,9]. The CDR1 and CDR2, which are encoded within the V region genes, interact predominantly with the HLA molecule [10]. The CDR3 spans the junction of the V(D)J segments and interacts with the peptide antigen [10,11].…”

“…The CDR1 and CDR2, which are encoded within the V region genes, interact predominantly with the HLA molecule [10]. The CDR3 spans the junction of the V(D)J segments and interacts with the peptide antigen [10,11]. The diversity of the CDR3 is generated by the mechanisms that join the V(D)J segments during the maturation of the T cell [12].…”