A strong propensity toward loop formation characterizes the expressed reading frames of the D segments at the Ig H and T cell receptor loci

Abstract

A compilation of murine and human Ig H and TcR beta D segment sequences was used to estimate the relative usage of the various reading frames and to look for associated sequence patterns. We confirm a strong bias in the expression of the Ig H D segments, with more than 90% (murine) and 85% (human) expressed peptides resulting from a preferred reading frame. Remarkably, 86% (mouse) and 90% (human) of those peptides contain at least one glycine residue. All but one of the atypical preferred D peptides contain serine or proline residues and are found in the immediate vicinity of glycine residues provided by specific JH segments. The presence of tyrosine residues is also a characteristic feature of expressed reading frames in both mouse (75%) and human (90%). These results suggest that the constraints of forming a flexible loop within the third complementarity-determining region, is a factor in the preference for a particular reading frame in Ig H D. For the TcR beta D segments, glycine is specified in most reading frames, and no significant preference is observed.

B precursor acute lymphoblastic leukemia third complementarity‐determining regions predominantly represent an unbiased recombination repertoire: Leukemic transformation frequently occurs in fetal life

“…Indeed the DA and DM D genes, which are infrequently rearranged, appear to be preferentially selected into the peripheral B cell pool (Table 2). These data support the hypothesis that in humans Dreading-frame preferences are primarily due to constraints of forming a flexible loop within the third complementarity determining region [40].Therefore, it seems unlikely that a selection mechanism based on D reading frame at the progenitor B cell stage of differentiation, as described for the mouse [lo], plays a significant role in human B cell development.…”

Broad Cross-Reactive TCR Repertoires Recognizing Dissimilar Epstein-Barr and Influenza A Virus Epitopes

“…These non-template-encoded poly-Gly/Ala runs in the CDR3 of influenza A M1-specific memory pool are significantly enriched over that in naïve thymocytes, suggesting that these clones are preferentially selected during peripheral antigen exposure. The presence of these poly-Gly/Ala runs in the CDR3 of α- and β-chains might provide enhanced TCR flexibility and the ability to accommodate interaction with multiple epitopes (39, 40). …”

Isolation of Picomolar Affinity Anti-c-erbB-2 Single-chain Fv by Molecular Evolution of the Complementarity Determining Regions in the Center of the Antibody Binding Site

“…One possible explanation is that the disulfide bond formed by the cysteine residues stabilizes this region of the V H CDR3. Regardless, five of the 33 D gene segments encode a CXXXXC or CXXXC (Kabat et al, 1991) in the preferred reading frame (Yamada et al, 1991;Abergel & Claverie, 1991) suggesting that the motif has useful properties as a component of the primary immune repertoire. If so, then use of similar motifs could prove useful in construction of semi-synthetic antibody libraries (Hoogenboom & Winter, 1992).…”