Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease Activity.

Background: PR3-ANCA vasculitis has a genetic association with HLA-DPB1. We explored immunologic and clinical features related to the interaction of HLA-DPB1*04:01 with a strongly binding PR3 peptide epitope (PR3).

Methods: Patients with ANCA vasculitis with active disease and disease in remission were followed longitudinally.

Restricted myeloperoxidase epitopes drive the adaptive immune response in MPO-ANCA vasculitis.

Background: Treatment of autoimmune diseases has relied on broad immunosuppression. Knowledge of specific interactions between human leukocyte antigen (HLA), the autoantigen, and effector immune cells, provides the foundation for antigen-specific therapies. These studies investigated the role of HLA, specific myeloperoxidase (MPO) epitopes, CD4 T cells, and ANCA specificity in shaping the immune response in patients with anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis.

The oncoprotein TBX3 is controlling severity in experimental arthritis.

Background: Development of autoimmune diseases is the result of a complex interplay between hereditary and environmental factors, with multiple genes contributing to the pathogenesis in human disease and in experimental models for disease. The T-box protein 3 is a transcriptional repressor essential during early embryonic development, in the formation of bone and additional organ systems, and in tumorigenesis.

Methods: With the aim to find novel genes important for autoimmune inflammation, we have performed genetic studies of collagen-induced arthritis (CIA), a mouse experimental model for rheumatoid arthritis.

Determination of a Predictive Cleavage Motif for Eluted Major Histocompatibility Complex Class II Ligands.

CD4 T cells have a major role in regulating immune responses. They are activated by recognition of peptides mostly generated from exogenous antigens through the major histocompatibility complex (MHC) class II pathway. Identification of epitopes is important and computational prediction of epitopes is used widely to save time and resources.

Predicting HLA CD4 Immunogenicity in Human Populations.

Background: Prediction of T cell immunogenicity is a topic of considerable interest, both in terms of basic understanding of the mechanisms of T cells responses and in terms of practical applications. HLA binding affinity is often used to predict T cell epitopes, since HLA binding affinity is a key requisite for human T cell immunogenicity. However, immunogenicity at the population it is complicated by the high level of variability of HLA molecules, potential other factors beyond HLA as well as the frequent lack of HLA typing data.

Accurate pan-specific prediction of peptide-MHC class II binding affinity with improved binding core identification.

A key event in the generation of a cellular response against malicious organisms through the endocytic pathway is binding of peptidic antigens by major histocompatibility complex class II (MHC class II) molecules. The bound peptide is then presented on the cell surface where it can be recognized by T helper lymphocytes. NetMHCIIpan is a state-of-the-art method for the quantitative prediction of peptide binding to any human or mouse MHC class II molecule of known sequence.

NetMHCIIpan-3.0, a common pan-specific MHC class II prediction method including all three human MHC class II isotypes, HLA-DR, HLA-DP and HLA-DQ.

Major histocompatibility complex class II (MHCII) molecules play an important role in cell-mediated immunity. They present specific peptides derived from endosomal proteins for recognition by T helper cells. The identification of peptides that bind to MHCII molecules is therefore of great importance for understanding the nature of immune responses and identifying T cell epitopes for the design of new vaccines and immunotherapies.

Bioinformatics identification of antigenic peptide: predicting the specificity of major MHC class I and II pathway players.

Bioinformatics methods for immunology have become increasingly used over the last decade and now form an integrated part of most epitope discovery projects. This wide usage has led to the confusion of defining which of the many methods to use for what problems. In this chapter, an overview is given focusing on the suite of tools developed at the Technical University of Denmark.

NetMHCcons: a consensus method for the major histocompatibility complex class I predictions.

A key role in cell-mediated immunity is dedicated to the major histocompatibility complex (MHC) molecules that bind peptides for presentation on the cell surface. Several in silico methods capable of predicting peptide binding to MHC class I have been developed. The accuracy of these methods depends on the data available characterizing the binding specificity of the MHC molecules.