Quantitative online prediction of peptide binding to the major histocompatibility complex

With its implications for vaccine discovery, the accurate prediction of T cell epitopes is one of the key aspirations of computational vaccinology. We have developed a robust multivariate statistical method, based on partial least squares, for the quantitative prediction of peptide binding to major histocompatibility complexes (MHC), the principal checkpoint on the antigen presentation pathway. As a service to the immunobiology community, we have made a Perl implementation of the method available via a World Wide Web server. We call this server MHCPred. Access to the server is freely available from the URL: http://www.jenner.ac.uk/MHCPred. We have exemplified our method with a model for peptides binding to the common human MHC molecule HLA-B*3501.

Immunological protein-protein interactions:a critical reflection

Life, and the biochemistry of which it is ultimately comprised, is built from the interactions of proteins, and the study of protein-protein interactions is fast becoming a central feature of molecular bioscience. This is as true of immunobiology as it is of other areas of the wider biological milieu. Protein-protein interactions within an immunological setting comprise both the kind familiar from other areas of biology and instantiations of protein-protein interactions special to the immune arena. Of the generic kind of protein-protein interaction, co-stimulatory receptors, such as CD28, and the interaction of accessory proteins, such as CD4 or CD8, are amongst the most prevalent and apposite of examples. The key examples of special immunological instantiations of protein-protein interactions are the binding of antigens by antibodies and the formation of peptide-MHC-TCR complexes; both prime examples of vital molecular recognition events mediated by protein-protein interactions. In this brief review, and within the context of this burgeoning field, we examine immunological protein-protein interactions, focussing on the problematic nature of defining such interactions. © 2011 by Nova Science Publishers, Inc. All rights reserved.

Outcomes after Unrelated Umbilical Cord Blood Transplantation for Children with Osteopetrosis.

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for most children with osteopetrosis (OP). Timing of HSCT is critical; therefore, umbilical cord blood transplantation (UCBT) is an attractive option. We analyzed outcomes after UCBT in 51 OP children. Median age at UCBT was 6 months. Seventy-seven percent of the cord blood grafts had 0 or 1 HLA disparity with the recipient. Conditioning regimen was myeloablative (mostly busulfan-based in 84% and treosulfan-based in 10%). Antithymocyte globulin was given to 90% of patients. Median number of total nucleated and CD34(+) cells infused was 14 × 10(7)/kg and 3.4 × 10(5)/kg, respectively. Median follow-up for survivors was 74 months. Cumulative incidence (CI) of neutrophil recovery was 67% with a median time to recovery of 23 days; 33% of patients had graft failure, 81% of engrafted patients had full donor engraftment, and 19% had mixed donor chimerism. Day 100 CI of acute graft-versus-host disease (grades II to IV) was 31% and 6-year CI of chronic graft-versus-host disease was 21%. Mechanical ventilation was required in 28%, and veno-occlusive disease was diagnosed in 16% of cases. Six-year overall survival rate was 46%. Comparative studies with other alternative donors should be performed to evaluate whether UCBT remains a valid alternative for children with OP without an HLA-matched donor.