Simultaneous expression of CD4 and CD8 antigens by a substantial proportion of resting porcine T lymphocytes

The existence of four subpopulations in resting porcine T lymphocytes is documented. In addition to the two known subpopulations which are typified by a mutually exclusive expression of either the CD8 or the CD4 differentiation antigen, CD4-CD8+ and CD4+CD8- T lymphocytes, respectively, two unusual subpopulations were prominent not only in peripheral blood, but also in lymphoid tissues: CD4-CD8- T lymphocytes expressing neither of these antigens and CD4+CD8+ T lymphocytes coexpressing both antigens. While CD4+CD8+ lymphoblasts have been found also in other species, resting T lymphocytes with that phenotype are without precedent among all species analyzed to date. This unique composition of the porcine T lymphocyte population has to be taken into consideration when the swine is used as a large animal model in experimental medicine

Uniting Foes of a Single Nation: Religious Dispute Resolution for India and Pakistan

This article will bring forth the argument that a religious-based dispute resolution mechanism should be employed to, at a bare minimum, build bridges between the two countries that are dominated by Hinduism and Islam. This article is not suggesting that religious-based dispute resolution will be a panacea to the India-Pakistan conflict, but simply a method of putting the countries on a step towards reconciliation. Section II of the article will detail the historical background of the conflict. Section III will highlight existing ADR in both India and Pakistan. Section IV will go over the Islamic perspective on dispute resolution. Section V will review the Hindu method of dispute resolution. Section VI will explain how commonalities between Hindu and Islamic dispute resolution can mitigate the hostilities between the peoples of India and Pakistan. Finally, Section VII will conclude the article

PEPVAC: a web server for multi-epitope vaccine development based on the prediction of supertypic MHC ligands

Prediction of peptide binding to major histocompatibility complex (MHC) molecules is a basis for anticipating T-cell epitopes, as well as epitope discovery-driven vaccine development. In the human, MHC molecules are known as human leukocyte antigens (HLAs) and are extremely polymorphic. HLA polymorphism is the basis of differential peptide binding, until now limiting the practical use of current epitope-prediction tools for vaccine development. Here, we describe a web server, PEPVAC (Promiscuous EPitope-based VACcine), optimized for the formulation of multi-epitope vaccines with broad population coverage. This optimization is accomplished through the prediction of peptides that bind to several HLA molecules with similar peptide-binding specificity (supertypes). Specifically, we offer the possibility of identifying promiscuous peptide binders to five distinct HLA class I supertypes (A2, A3, B7, A24 and B15). We estimated the phenotypic population frequency of these supertypes to be 95%, regardless of ethnicity. Targeting these supertypes for promiscuous peptide-binding predictions results in a limited number of potential epitopes without compromising the population coverage required for practical vaccine design considerations. PEPVAC can also identify conserved MHC ligands, as well as those with a C-terminus resulting from proteasomal cleavage. The combination of these features with the prediction of promiscuous HLA class I ligands further limits the number of potential epitopes. The PEPVAC server is hosted by the Dana-Farber Cancer Institute at the site

Forward Vaccinology: CTL Targeting Based upon Physical Detection of HLA-Bound Peptides

Vaccine-elicited cytotoxic T lymphocytes (CTL) recognizing conserved fragments of a pathogen’s proteome could greatly impact infectious diseases and cancers. Enabling this potential are recent advances in mass spectrometry that identify specific target peptides among the myriad HLA-bound peptides on altered cells. Ultrasensitivity of these physical detection methods allows for the direct assessment of peptide presentation on small numbers of tissue-derived cells. In addition, concurrent advances in immunobiology suggest ways to induce CTLs with requisite functional avidity and tissue deployment. Elicitation of high-avidity resident-memory T cells through vaccination may shift the vaccinology paradigm both for preventive and therapeutic approaches to human disease control

Molecular Detection of Targeted Major Histocompatibility Complex I-Bound Peptides Using a Probabilistic Measure and Nanospray MS3 on a Hybrid Quadrupole-Linear Ion Trap

A nanospray MS3 method deployed on a quadrupole linear ion trap hybrid can detect targeted peptides with high dynamic range and high sensitivity from complex mixtures without separations. The method uses a recognition algorithm that is a modification of the relative (Kullback−Leibler, KL) entropy characterization of probabilistic distance to detect if reference MS3 fragmentation patterns are components of acquired MS3 spectra. The recognition reflects the probabilistic structure of physical MS measurements unlike the Euclidean or inner product metrics widely used for comparing spectra. It capably handles spectra with a significant chemical ion background in contrast to the Euclidean metric or the direct relative entropy. The full nanospray MS3 method allows both the detection and quantitation of targets without the need to obtain isotopically labeled standards. By avoiding chromatographic separations and its associated surface losses, the detection can be applied to complex samples on a very limited material scale. The methodology is illustrated by applications to the medically important problem of detecting targeted major histocompatibility complex (MHC) I associated peptides extracted from limited cell numbers