The effect of anchor residue modifications on the stability of major histocompatibility complex class I-peptide interactions

Anchor residues in peptides determine the specificity of binding to major histocompatibility complex class I molecules through interactions of their side chains with pockets in the peptide-binding groove. We have compared the kinetics of association of a Sendai virus nucleoprotein-derived peptide (FAPGNYPAL, termed SV9) with H-2K^b class I molecules, and the same peptide iodinated on the anchor residue tyrosine (¹²⁵I-SV9). Even though the association rates were too rapid for direct measurements, competition studies indicated that they were similar for SV9 and ¹²⁵I-SV9. To measure the binding of non-radioactive SV9 directly, SV9 was tritiated (³H-SV9). ³H-SV9 remained stably associated with H-2K^b molecules, whereas ¹²⁵I-SV9 dissociated in a temperature-dependent fashion. Thus, modifications on anchor residues do not necessarilly have to affect the specificity and association kinetics of peptide binding to class I molecules but can affect the stability of the resulting class I-peptide interaction. The dissociation of peptides with modified and, more generally, suboptimal anchor residue side chains may explain the presence of empty class I molecules and free class I heavy chains at the cell surface.     

Can capsular plication compensate the lack of one suture anchor in an arthroscopic three suture anchor Bankart repair? A comparative study

ObjectiveThe aim of this study was to compare the complication rates and clinical results of labral repair with two suture anchors and capsular plication, and labral repair with three suture anchor fixation in artroscopic Bankart surgery.MethodsSixty-nine patients (60 males, 9 females; mean age: 28.2 ± 7.8 years (range: 16–50)) who had undergone arthroscopic repair of a labral Bankart lesion were evaluated. Group A underwent an arthroscopic Bankart repair with three knotless suture anchors, while group B underwent a modified arthroscopic Bankart repair with two knotless suture anchors and an additional capsular plication procedure. The mean follow-up was 52.5 months. Constant Shoulder Score (CSS), Rowe Score (RS), modified UCLA Shoulder Score (mUSS) and range of motion (ROM) were used as outcome measures.ResultsIn both groups, a significant improvement was detected in functional outcomes at postoperative last follow-up compared to the preoperative period. No statistically significant difference was found (p > 0.05) in clinical scores (CSS; Group A: 89.7, Group B: 80.2) (RS; Group A: 88.2, Group B: 80.2) (mUSS; Group A: 26.3, Group B: 25.7) external rotation loss (At neutral; Group A: 4.5°, Group B: 5.2°. At abduction; Group A: 4.3°, Group B: 5.7°) and recurrence rates (Group A: 13.3%, Group B: 20.8%). Although the difference was not statistically significant, the recurrence rate was higher in group B (20.8%), compared to group A (13.3%), despite the shorter average follow-up time of group B (p = 0.417).ConclusionsArthroscopic repair of labral Bankart lesions with both techniques showed good functional outcomes and stability at the latest follow-up. Higher recurrence rate despite the shorter average follow-up of group B suggests that two anchor usage might not be sufficient for Bankart repair in terms of better stability and less recurrence risk.Level of evidenceLevel III, Therapeutic Study.     

Endangered mothers or ‘anchor babies’? Migration motivators for pregnant unaccompanied Central American teens

As politicians grapple with global migration policies, traditionally sympathetic populations such as pregnant migrant women now evoke suspicion and fear, evident in US usage of the disparaging term ‘anchor babies.’ Using secondary interview data, this article compares the migration motivations of 11 pregnant unaccompanied teens from Honduras, El Salvador, and Guatemala with the ‘anchor baby’ assumptions. Results reveal migration motivation themes of safety concerns, desire for US opportunities, and assistance of a US-based relative. Nine of the 11 teens revealed safety concerns for themselves or their child, largely as a consequence of sexual and gender-based violence. A beginning model of migration for pregnant Central American teens is proposed. Practice implications include sensitivity to the possibility of sexual and gender based violence prior to migration, use of varied questioning to reveal such experiences, the connection between safety concerns and US legal protections, and the need to debunk erroneous political rhetoric.     

The CD4+ T‐cell epitope‐binding register is a critical parameter when generating functional HLA‐DR tetramers with promiscuous peptides

Detection of CD4⁺ T cells specific for tumor‐associated antigens is critical to investigate the spontaneous tumor immunosurveillance and to monitor immunotherapy protocols in patients. We investigated the ability of HLA‐DR^*1101 multimers to detect CD4⁺ T cells specific for three highly promiscuous MAGE‐A3 derived peptides: MAGE‐A3_191–205 (p39), MAGE‐A3_281–295 (p57) and MAGE‐A3_286–300 (p58). Tetramers stained specific CD4⁺ T cells only when loaded with p39, although all peptides activated the specific T cells when presented by plastic‐bound HLA‐DR^*1101 monomers. This suggested that tetramer staining ability was determined by the mode rather than the affinity of peptide binding to HLA‐DR^*1101. We hypothesized that peptides should bear a single P1 anchor residue to bind all arms of the multimer in a homogeneous register to generate peptide‐HLA‐DR conformers with maximal avidity. Bioinformatics analysis indicated that p39 contained one putative P1 anchor residue, whereas the other two peptides contained multiple ones. Designing p57 and p58 analogues containing a single anchor residue generated HLA‐DR^*1101 tetramers that stained specific CD4⁺ T cells. Producing HLA‐DR^*1101 monomers linked with the optimized MAGE‐A3 analogues, but not with the original epitopes, further improved tetramer efficiency. Optimization of CD4⁺ T‐cell epitope‐binding registers is thus critical to generate functional HLA‐DR tetramers.     

Fryns Syndrome Associated with Recessive Mutations in PIGN in two Separate Families

Fryns syndrome is an autosomal recessive condition characterized by congenital diaphragmatic hernia (CDH), dysmorphic facial features, distal digital hypoplasia, and other associated malformations, and is the most common syndromic form of CDH. No gene has been associated with this condition. Whole‐exome sequence data from two siblings and three unrelated individuals with Fryns syndrome were filtered for rare, good quality, coding mutations fitting a recessive inheritance model. Compound heterozygous mutations in PIGN were identified in the siblings, with appropriate parental segregation: a novel STOP mutation (c.1966C>T: p.Glu656X) and a rare (minor allele frequency <0.001) donor splice site mutation (c.1674+1G>C) causing skipping of exon 18 and utilization of a cryptic acceptor site in exon 19. A further novel homozygous STOP mutation in PIGN (c.694A>T: p.Lys232X) was detected in one unrelated case. All three variants affected highly conserved bases. The two remaining cases were negative for PIGN mutations. Mutations in PIGN have been reported in cases with multiple congenital anomalies, including one case with syndromic CDH. Fryns syndrome can be caused by recessive mutations in PIGN. Whether PIGN affects other syndromic and non‐syndromic forms of CDH warrants investigation.     

标准冠内固位体在口腔固定修复领域中的初步应用

目的：探讨成品专用固位体在口腔修复领域中应用的可行性。方法：用荷兰产微型气动弯手机和特制钻头在缺牙两侧基牙近远中面钻孔。将成品专用钛合金冠内固位体粘接在基牙邻面上，制取精确印模，灌制带专用固位体代型的工作模型，铸造抗力桥架并烤瓷人造牙制作固定桥，并将此固位体用于固位条件不良的全冠、桩冠、种植义齿的辅助固位。结果：共制作188例各类固定修复体，其中无冠式固定桥98例，配合全冠制作的固定桥62例，桩冠20例，人工种植牙1例，全冠7例。因适应症选择不当或不规范操作造成在20个月内共6例无冠式固定桥发生松动脱落。结论：此法具有磨牙少、痛苦小、省时简便等优点。也可用于辅助固位。