Constitutional Law - Abortion - Father\u27s Rights

The Supreme Court of Massachusetts has denied injunctive and declaratory relief to a father seeking to restrain the mother of his child from procuring an abortion. Doe v. Doe, 314 N.E.2d 128 (Mass. 1974)

TAPBPR: a new player in the MHC class I presentation pathway.

In order to provide specificity for T cell responses against pathogens and tumours, major histocompatibility complex (MHC) class I molecules present high-affinity peptides at the cell surface to T cells. A key player for peptide loading is the MHC class I-dedicated chaperone tapasin. Recently we discovered a second MHC class I-dedicated chaperone, the tapasin-related protein TAPBPR. Here, we review the major steps in the MHC class I pathway and the TAPBPR data. We discuss the potential function of TAPBPR in the MHC class I pathway and the involvement of this previously uncharacterised protein in human health and disease.C.H was supported by a Wellcome Trust PhD Studentship (Grant 089563) and L.H.B was funded by a Wellcome Trust Career Development Fellowship (Grant 085038).This is the author accepted manuscript. The final published version is available via Wiley at http://onlinelibrary.wiley.com/doi/10.1111/tan.12538/abstract;jsessionid=3D6AF64F5BD8C64E84634A4303842BE2.f04t01

Allelic polymorphism in the T cell receptor and its impact on immune responses

In comparison to human leukocyte antigen (HLA) polymorphism, the impact of allelic sequence variation within T cell receptor (TCR) loci is much less understood. Particular TCR loci have been associated with autoimmunity, but the molecular basis for this phenomenon is undefined. We examined the T cell response to an HLA-B*3501-restricted epitope (HPVGEADYFEY) from Epstein-Barr virus (EBV), which is frequently dominated by a TRBV9*01 public TCR (TK3). However, the common allelic variant TRBV9*02, which differs by a single amino acid near the CDR2β loop (Gln55→His55), was never used in this response. The structure of the TK3 TCR, its allelic variant, and a nonnaturally occurring mutant (Gln55→Ala55) in complex with HLA-B*3501 revealed that the Gln55→His55 polymorphism affected the charge complementarity at the TCR-peptide-MHC interface, resulting in reduced functional recognition of the cognate and naturally occurring variants of this EBV peptide. Thus, polymorphism in the TCR loci may contribute toward variability in immune responses and the outcome of infection

Intergranular Corrosion-Fatigue Failure of Cobalt-Alloy Femoral Stems. A Failure Analysis of Two Implants

Two modular hip implants with a cobalt-alloy head and a cobalt-alloy stem were retrieved after a fracture had occurred in the neck region of the femoral component, eighty-five and seventy months after implantation. Both implants failed less than one millimeter distal to the taper junction between the head and the stem (outside of the taper). The fracture surfaces of the implant were investigated with the use of scanning electron microscopy, to determine the nature of the failure process. The fractures occurred at the grain boundaries of the microstructure and appeared to be the result of three factors: porosity at the grain boundaries; intergranular corrosive attack, initiated both at the head-neck taper and at the free surface; and cyclic fatigue-loading of the stem. The corrosive attack of the free surface was initiated, in part, by the egression of surface grains and by the ingression of fluid into the intergranular regions. Sectioned surfaces showed extensive intergranular corrosive attack in the prosthetic neck localized in the region of the head-neck taper junction and penetrating deeply into the microstructure

Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion

HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion

Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell–mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR–HLA-B*4405EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes