Pullularins E and F, two new peptides from the endophytic fungus Bionectria ochroleuca isolated from the mangrove plant Sonneratia caseolaris

Acknowledgements This project was supported by grants of the BMBF (to P.P.) and MOST (to W.L.). We wish to thank W.E.G. Müller (Johannes-Gutenberg-University, Mainz, Germany) for carrying out the cytotoxicity assay. A scholarship (Grant No. 10/6/117) granted and financed by the Egyptian Government (Ministry of High Education) to W.E. is gratefully acknowledged.Peer reviewedPublisher PD

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

T cell allorecognition and MHC restriction—A case of Jekyll and Hyde?

A great paradox in cellular immunology is how T cell allorecognition exists at high frequencies (up to 10%) despite the stringent requirements of discriminating ‘self’ from ‘non-self’ imposed by MHC restriction. Thus, in tissue transplantation, a substantial proportion of the recipient's T cells will have the ability to recognize the graft and instigate an immune response against the transplanted tissue, ultimately resulting in graft rejection—a manifestation of T cell alloreactivity. Transplantation of human organs and lymphoid cells as treatment for otherwise life-threatening diseases has become a more routine medical procedure making this problem of great importance. Immunologists have gained important insights into the mechanisms of T cell alloreactivity from cytotoxic T cell assays, affinity-avidity studies, and crystal structures of peptide-MHC (pMHC) molecules and T cell receptors (TCRs) both alone and in complex. Despite the clinical significance of alloreactivity, the crystal structure of an alloreactive human TCR in complex with both cognate pMHC and an allogeneic pMHC complex has yet to be determined. This review highlights some of the important findings from studies characterizing the way in which alloreactive T cell receptors and pMHC molecules interact in an attempt to resolve this great irony of the cellular immune response

T Cell Allorecognition via Molecular Mimicry

SummaryT cells often alloreact with foreign human leukocyte antigens (HLA). Here we showed the LC13 T cell receptor (TCR), selected for recognition on self-HLA-B∗0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B∗4402 and HLA-B∗4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B∗0801, HLA-B∗4402, and HLA-B∗4405 and the disparate sequences of the viral and allopeptides, the LC13 TCR engaged these peptide-HLA (pHLA) complexes identically, accommodating mimicry of the viral peptide by the allopeptide. The viral and allopeptides adopted similar conformations only after TCR ligation, revealing an induced-fit mechanism of molecular mimicry. The LC13 T cells did not alloreact against HLA-B∗4403, and the single residue polymorphism between HLA-B∗4402 and HLA-B∗4403 affected the plasticity of the allopeptide, revealing that molecular mimicry was associated with TCR specificity. Accordingly, molecular mimicry that is HLA and peptide dependent is a mechanism for human T cell alloreactivity between disparate cognate and allogeneic pHLA complexes

Methods for isolation of marine-derived endophytic fungi and their bioactive secondary products

Marine-derived fungi have been shown in recent years to produce a plethora of new bioactive secondary metabolites, some of them featuring new carbon frameworks hitherto unprecedented in nature. These compounds are of interest as new lead structures for medicine as well as for plant protection. The aim of this protocol is to give a detailed description of methods useful for the isolation and cultivation of fungi associated with various marine organisms (sponges, algae and mangrove plants) for the extraction, characterization and structure elucidation of biologically active secondary metabolites produced by these marine-derived endophytic fungi, and for the preliminary evaluation of their pharmacological properties based on rapid 'in house' screening systems. Some results exemplifying the positive outcomes of the protocol are given at the end. From sampling in marine environment to completion of the structure elucidation and bioactivity screening, a period of at least 3 months has to be scheduled