Certain "protective" major histocompatibility complex class I (MHC-I) alleles, such as B*57 and B*27, are associated with long-term control of HIV-1 in vivo mediated by the CD8+ cytotoxic-T-lymphocyte (CTL) response. However, the mechanism of such superior protection is not fully understood. Here we combined high-throughput fitness profiling of mutations in HIV-1 Gag, in silico prediction of MH...

Natural killer (NK) cells express inhibiting receptors (iNKRs), which specifically bind MHC-I molecules on the surface of healthy cells. When the expression of MHC-I on the cell surface decreases, which might occur during certain viral infections and cancer, iNKRs lose inhibiting signals and the infected cells become target for NK cell activation (missing-self detection). Although the detection...

Proteins show drastic discrepancies in their contribution to the collection of self-peptides that shape the repertoire of CD8 T cells (MHC I self-immunopeptidome). To decipher why selected proteins are the foremost sources of MHC I-associated self-peptides, we chose to study SIMP/STT3B because this protein generates very high amounts of MHC I-associated peptides in mice and humans. We show that...

Cancer cells develop under immune surveillance, thus necessitating immune escape for successful growth. Loss of MHC class I expression provides a key immune evasion strategy in many cancers, although the molecular mechanisms remain elusive. MHC class I transactivator (CITA), known as "NLRC5" [NOD-like receptor (NLR) family, caspase recruitment (CARD) domain containing 5], has recently been iden...

The threshold for systemic viral infection relies on the amplification of virus at a primary infection site. We have identified that class I MHC molecules can trigger the inhibition of replication of Sindbis virus in a haplotype- and allele-specific manner. Class I MHC molecules of H-2d haplotypes exhibit a strong inhibitory effect whereas H-2k haplotypes show minimal inhibition of Sindbis vira...

Proteins of the major histocompatibility complex class I (MHC class I) are best known for their central role in the immune response. However, accumulating evidence shows that MHC class I proteins also have nonimmune roles in the healthy nervous system. MHC class I is expressed by developing and adult neurons, and is required for the proper establishment, function and modification of synaptic co...

MHC class I proteins mediate functions in anti-pathogen defense. MHC diversity has already been investigated by many studies in model avian species, but here we chose the bar-headed goose, a worldwide migrant bird, as a non-model avian species. Sequences from exons encoding the peptide-binding region (PBR) of MHC class I molecules were isolated from liver genomic DNA, to investigate variation i...

The activity of NK cells is regulated by activating receptors that recognize mainly stress-induced ligands and by inhibitory receptors that recognize mostly MHC class I proteins on target cells. Comparing the cytoplasmic tail sequences of various MHC class I proteins revealed the presence of unique cysteine residues in some of the MHC class I molecules which are absent in others. To study the r...

MHC class I molecules present peptides derived primarily from endogenously synthesized proteins on the cell surface as ligands for CD8+ T cells. However, CD8+ T cell responses to extracellular bacteria, virus-infected, or tumor cells can also be elicited because certain professional APC can generate peptide/MHC class I (MHC-I) complexes from exogenous sources. Whether the peptide/MHC-I complexe...

HLA-F has low levels of polymorphism in humans and is highly conserved among primates, suggesting a conserved function in the immune response. In this study, we probed the structure of HLA-F on the surface of B lymphoblastoid cell lines and activated lymphocytes by direct measurement of peptide binding to native HLA-F. Our findings suggested that HLA-F is expressed independently of bound peptid...