Current Pharmaceutical Design - Volume 15, Issue 28, 2009

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T cell immune responses are driven by the recognition of peptide antigens (T cell epitopes) that are bound to major histocompatibility complex (MHC) molecules. T cell epitope immunogenicity is thus contingent on several events, including appropriate and effective processing of the peptide from its protein source, stable peptide binding to the MHC molecule, and recognition of the MHC-bound peptide by the T cell receptor. O Read More

Short peptides derived from cellular proteins may escape complete destruction during protein catabolism and finally serve as a showcase in the immune system. Exposed at the cell surface to scrutiny by T cells, MHC:peptide complexes mediate a highly specific and immediate information transfer from diseased cells to the cellular immune system. Numerous clinical vaccination trials have been carried out employing MHC-p Read More

Vaccination techniques have developed rapidly over the last several decades from the immunization with live attenuated pathogens to the use of peptide and DNA subunit vaccines, from the use of classical adjuvants to cell-directed delivery. Vaccination techiques are also under investigation for the treatment of tumors and autoimmune diseases. However, profound knowledge of activation mechanisms of the immune cells on Read More

Vaccines are one of the most cost effective methods to control infectious diseases and at the same time one of the most complex products of the pharmaceutical industry. In contrast to other drugs, vaccines are used mainly in healthy individuals, often in children. For this reason, very high standards are set for their production. Subunit vaccines, especially peptide vaccines, can provide a safe and cost-effective alternative to Read More

The Major Histocompatibility Complex Class II locus is the primary genetic linkage to autoimmune diseases. Susceptibility to each such disease is linked to different alleles, with a few alleles showing also dominant protection. The design of vaccines for autoimmune diseases is a long sought-after goal. As knowledge about the pathogenesis of these diseases has increased, the tools for such an approach have of necessity bee Read More

Central to the initiation of a T cell dependent immune response is the recognition of major histocompatibility complex (MHC) class I or class II molecules (in humans termed HLA and in mice termed H-2) bound to antigenic peptide. T cell receptors (TCR) have programmed specificity for particular peptide/MHC complexes, which ensures focused immune responses are generated against the antigen source. To design effec Read More

What makes a peptide an epitope? This is a central question in immunology. The clear identification of precise molecular characteristics of epitopes would help define the basic mechanisms of self/non-self distinction and lead to a greater understanding of phenomena such as tolerance, autoimmunity, allergy, and tumor escape of immune surveillance. Importantly, clarifying the properties an epitope is paramount to the Read More

The success of vaccination is directly or indirectly based on the specificity of antigen recognition by T lymphocytes, their efficient activation and expansion, and the generation of vaccine-specific effector and memory cells. These traits are largely dependent on the correct assembly and expression of sufficient number of functional TCR/CD3 complexes in the cell surface. In this review, some of the genetic and epigenetic f Read More

MHC-specific Natural Killer inhibitory receptors display a conserved and fundamental function in the regulation of NK-mediated cytolysis. Their importance is substantiated by the fact that during speciation different molecular receptor structures have evolved to maintain inhibitory regulation of NK cells. The information gained during these last twenty years begins to be fruitfully used in the therapy of leukemias, but a lot has t Read More

CD1 molecules are a family of non-polymorphic, class I antigen-presenting glycoproteins, which bind and present amphiphilic lipid antigens for recognition to T cells. Two groups of CD1 molecules are involved in presentation of self and foreign lipid antigens: group 1 (CD1a, CD1b and CD1c) and group 2 (CD1d). Crystal structures of CD1a, CD1b and CD1d in complex with different ligands have revealed the key principles of lipi Read More

Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule, which was first discovered in 1987 by Geraghty and colleagues [1]. While classical HLA class I molecules are expressed on all nucleated cells, the expression of the HLA-G molecule is highly tissue-restricted, such as to placental trophoblast cells. HLA-G binds inhibitory receptors such as leukocyte immunoglobulin-like receptors B1 (LILRB1/ILT2/CD85j) Read More

In addition to a variety of other techniques used in T-cell epitope identification, mass spectrometery coupled to liquid chromatography have now become an important and sensitive tool in separation, detection, and sequence analysis of highly complex natural major histocompatibility complex (MHC) ligand mixtures. In this article, we present current strategies for the identification of MHC eluted peptides using high-performance Read More

In humans, major histocompatibility complex (MHC) class I molecules comprise the classical (class Ia) human leukocyte antigens (HLA)-A, -B, and -C, and the non-classical (class Ib) HLA-E, -F, -G and -H (HFE) molecules. The best-characterized MHC class Ib molecule is HLA-E. HLA-E was first described as a non-polymorphic ligand of the CD94/NKG2 receptors expressed mainly by natural killer (NK) cells and its role was thus co Read More