Most eukaryotic cells express major histocompatibility complex (MHC) class I molecules on their surface. These immune molecules present peptide fragments derived from the breakdown of proteins in the cell to CD8+ cytotoxic T lymphocytes (CTLs), which recognize the peptide–MHC complexes via T-cell receptors (TCRs) expressed on their surface [1]. In uninfected cells, the peptides that are bound w...

Genetic factors such as the MHC influence the immunocompetence of an individual. MHC genes are the most polymorphic genes in primates, which is often interpreted as an adaptation to establish good T cell responses to a wide range of (evolving) pathogens. Chimpanzee MHC (Patr) genes are less polymorphic than human MHC (HLA) genes, which is surprising because chimpanzee is the older species of th...

Distinguishing self from nonself and pathogenic from nonpathogenic is a fundamental challenge to the immune system but whether adaptive immune systems use pathogen-specific signatures to achieve this is largely unknown. By investigating the presentation of large sets of viruses and bacteria on MHC class I molecules, we analyze whether MHC-I molecules have a preference for pathogen-derived pepti...

Recognition of antigen by CD4 ϩ T cells requires presentation of short peptide fragments in the context of het-erodimeric MHC class II molecules (1, 2). Antigen presentation by MHC class II molecules is pivotal to the induction of adaptive immune responses, peripheral tolerance , and central tolerance, as well as being required for CD4 ϩ T cell survival (1–3). Constitutive expression of MHC cla...

BACKGROUND Major histocompatibility complex (MHC) class I molecules play key roles in host immunity against pathogens by presenting peptide antigens to CD8+ T-cells. Many variants of MHC molecules exist, and each has a unique preference for certain peptide ligands. Both experimental approaches and computational algorithms have been utilized to analyze these peptide MHC binding characteristics. ...

Diversity is a hallmark of the immune system. The repertoires of B cells and of CD4 and CD8 T cells each consist of more than 108 different clonotypes each characterized by a unique receptor. Each immune response is characterized by a large panel of different cytokines with –partly overlapping– functions. Each individual is characterized by a unique combination of MHC molecules that play an ess...

The hallmark of T lymphocyte recognition is combined specificity for self MHC molecules and nominal antigen, i.e ., MHC-restricted recognition. As a rule, cytotoxic T lymphocytes (Tc)' are restricted by class I MHC molecules (K, D, and L molecules in the mouse) (1, 2), whereas T helper lymphocyte (Th) recognition is restricted by class II MHC molecules (I-A and I-E molecules in the mouse) (3, 4...

The killer cell Ig-like receptors (KIRs) expressed on the surface of NK cells recognize specific MHC class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In HIV infection, survival is linked to host KIR and MHC-I genotypes. In the SIV macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions...

Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Marek's disease caused by ...

Recently, we revealed that TAPBPR is a peptide exchange catalyst that is important for optimal peptide selection by MHC class I molecules. Here, we asked whether any other co-factors associate with TAPBPR, which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calr...