Immunogenetics 

About: Immunogenetics is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Gene & Major histocompatibility complex. It has an ISSN identifier of 0093-7711. Over the lifetime, 5350 publications have been published receiving 163107 citations. The journal is also known as: immungenetics.

SYFPEITHI: database for MHC ligands and peptide motifs.

Abstract: The first version of the major histocompatibility complex (MHC) databank SYFPEITHI: database for MHC ligands and peptide motifs, is now available to the general public. It contains a collection of MHC class I and class II ligands and peptide motifs of humans and other species, such as apes, cattle, chicken, and mouse, for example, and is continuously updated. All motifs currently available are accessible as individual entries. Searches for MHC alleles, MHC motifs, natural ligands, T-cell epitopes, source proteins/organisms and references are possible. Hyperlinks to the EMBL and PubMed databases are included. In addition, ligand predictions are available for a number of MHC allelic products. The database content is restricted to published data only.

MHC ligands and peptide motifs: first listing.

Abstract: The purpose of this article is to provide a compendium of major histocompatibility complex (MHC) peptide motifs and MHC ligands known to date, together with a discussion of the methods used to gain this information. A problem here is the exponential growth of information in this field over the recent years. The number of known MHC ligands was zero in 1989 and three in 1990. This article, written in 1994, lists a couple of hundred such ligands, plus a large number of likely ligands. By the time this work is published, we expect a lot more ligands to be known. On the other hand, the peptide motifs of many of the more important MHC class I molecules are known already, so that this article will still be useful as a source of information. For class II, the situation is a bit different. Only a few allele-specific motifs have been reported, and the data from different authors are partially conflicting. The principles of allele-specific ligand motifs, however, have emerged recently by the combination of information on MHC class II structure, ligand sequencing, and peptide binding assays. Thus, these principles can be applied to further ligands to be identified.

NetMHCpan, a method for MHC class I binding prediction beyond humans

Abstract: Binding of peptides to major histocompatibility complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC genomic region (called HLA) is extremely polymorphic comprising several thousand alleles, each encoding a distinct MHC molecule. The potentially unique specificity of the majority of HLA alleles that have been identified to date remains uncharacterized. Likewise, only a limited number of chimpanzee and rhesus macaque MHC class I molecules have been characterized experimentally. Here, we present NetMHCpan-2.0, a method that generates quantitative predictions of the affinity of any peptide–MHC class I interaction. NetMHCpan-2.0 has been trained on the hitherto largest set of quantitative MHC binding data available, covering HLA-A and HLA-B, as well as chimpanzee, rhesus macaque, gorilla, and mouse MHC class I molecules. We show that the NetMHCpan-2.0 method can accurately predict binding to uncharacterized HLA molecules, including HLA-C and HLA-G. Moreover, NetMHCpan-2.0 is demonstrated to accurately predict peptide binding to chimpanzee and macaque MHC class I molecules. The power of NetMHCpan-2.0 to guide immunologists in interpreting cellular immune responses in large out-bred populations is demonstrated. Further, we used NetMHCpan-2.0 to predict potential binding peptides for the pig MHC class I molecule SLA-1*0401. Ninety-three percent of the predicted peptides were demonstrated to bind stronger than 500 nM. The high performance of NetMHCpan-2.0 for non-human primates documents the method’s ability to provide broad allelic coverage also beyond human MHC molecules. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan .

Human T-cell receptor variable gene segment families.

Abstract: Multiple DNA and protein sequence alignments have been constructed for the human T-cell receptor alpha/delta, beta, and gamma (TCRA/D, B, and G) variable (V) gene segments. The traditional classification into subfamilies was confirmed using a much larger pool of sequences. For each sequence, a name was derived which complies with the standard nomenclature. The traditional numbering of V gene segments in the order of their discovery was continued and changed when in conflict with names of other segments. By discriminating between alleles at the same locus versus genes from different loci, we were able to reduce the number of more than 150 different TCRBV sequences in the database to a repertoire of only 47 functional TCRBV gene segments. An extension of this analysis to the over 100 TCRAV sequences results in a predicted repertoire of 42 functional TCRAV gene segments. Our alignment revealed two residues that distinguish between the highly homologous V delta and V alpha, one at a site that in VH contacts the constant region, the other at the interface between immunoglobulin VH and VL. This site may be responsible for restricted pairing between certain V delta and V gamma chains. On the other hand, V beta and V gamma appear to be related by the fact that their CDR2 length is increased by four residues as compared with that of V alpha/delta peptides.

Nine major HLA class I supertypes account for the vast preponderance of HLA-A and -B polymorphism.

Abstract: Herein, we review the epitope approach to vaccine development, and discuss how knowledge of HLA supertypes might be used as a tool in the development of such vaccines. After reviewing the main structural features of the A2-, A3-, B7-, and B44- supertype alleles, and biological data demonstrating their immunological relevance, we analyze the frequency at which these supertype alleles are expressed in various ethnicities and discuss the relevance of those observations to vaccine development. Next, the existence of five new supertypes (A1, A24, B27, B58, and B62) is reported. As a result, it is possible to account for the predominance of all known HLA class I with only nine main functional binding specificities. The practical implications of this finding, as well as its relevance to understanding the functional implication of MHC polymorphism in humans, are discussed.