OGRDB: a reference database of inferred immune receptor genes

The immune rejection of allografts is mediated by T cells via two distinct pathways: the direct and the indirect pathways. Direct alloresponse to intact donor MHC molecules is ensured by T cells which are polyclonal and directed toward a variety of antigens. This response is highly sensitive to treatment by immunosuppressive drugs including Cyclosporin A. Indirect alloresponse is oligoclonal and involves a few dominant antigen peptides on donor MHC. In contrast to its direct counterpart, indirect allorecognition is thought to be poorly sensitive to blockade by cyclosporin A. It is likely that indirect and direct types of alloresponses play different roles in the physiology of the rejection process. T cell responses occurring via direct allorecognition play a critical role during the early phase of acute graft rejection by sensitizing the host to graft antigens. Alternatively, once such sensitization has taken place, indirect type of alloresponse may become predominant and presumably represent the driving force in the actual destruction of transplanted tissues. In addition, we and others have provided strong circumstantial evidence indicating that secondary T cell responses via indirect allorecognition spread to new determinants on donor MHC and tissue-specific antigens. This phenomenon is likely to play an important role in late and chronic rejection, a major obstacle to long-term graft acceptance in clinical transplantation. Finally, a series of studies have demonstrated that early, pre-transplant treatment with tolerogenic donor-derived MHC peptides can protect the graft from rejection in rodents. Although the mechanisms involved in MHC-peptide-induced tolerance are ill defined, this strategy represents a promising approach for ensuring long-lasting graft acceptance in the absence of widespread immunosuppression. It is now crucial to further explore the mechanims involved in immunogenicity and tolerogenicity of MHC peptides and to initiate clinical studies to evaluate the efficacy of blocking indirect alloresponses in transplanted patients

Monte Carlo phase diagram for diblock copolymer melts

The phase diagram for diblock copolymer melts is evaluated from lattice-based Monte Carlo simulations using parallel tempering, improving upon earlier simulations that used sequential temperature scans. This new approach locates the order-disorder transition (ODT) far more accurately by the occurrence of a sharp spike in the heat capacity. The present study also performs a more thorough investigation of finite-size effects, which reveals that the gyroid (G) morphology spontaneously forms in place of the perforated-lamellar (PL) phase identified in the earlier study. Nevertheless, there still remains a small region where the PL phase appears to be stable. Interestingly, the lamellar (L) phase next to this region exhibits a small population of transient perforations, which may explain previous scattering experiments suggesting a modulated-lamellar (ML) phase