The non-polymorphic MHC molecule Qa-1 and its human counterpart HLA-E present monomorphic signal peptides to innate receptors and thereby regulate lymphocyte activity. Under stress, this peptide... Show moreThe non-polymorphic MHC molecule Qa-1 and its human counterpart HLA-E present monomorphic signal peptides to innate receptors and thereby regulate lymphocyte activity. Under stress, this peptide content is replaced with a surprisingly diverse repertoire of novel peptides that are associated with heat-shock proteins, infectious agents or antigen processing defects. Show less
Hall, T. van; Oliveira, C.C.; Joosten, S.A.; Ottenhoff, T.H.M. 2010
The non-polymorphic MHC molecule Qa-1 and its human counterpart HLA E present monomorphic signal peptides to innate receptors and thereby regulate lymphocyte activity Under stress this peptide... Show moreThe non-polymorphic MHC molecule Qa-1 and its human counterpart HLA E present monomorphic signal peptides to innate receptors and thereby regulate lymphocyte activity Under stress this peptide content is replaced with a surprisingly diverse repertoire of novel peptides that are associated with heat-shock proteins infectious agents or antigen processing defects (C) 2010 Institut Pasteur Published by Elsevier Masson SAS All rights reserved Show less
Oliveira, C.C.; Veelen, P.A. van; Querido, B.; Ru, A. de; Sluijter, M.; Laban, S.; ... ; Hall, T. van 2010
The nonclassical major histocompatibility complex (MHC) Qa-1b accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural... Show moreThe nonclassical major histocompatibility complex (MHC) Qa-1b accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural killer cells and CD8+ T cells. We here describe that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen-processing pathway. This novel peptide repertoire represents immunogenic neoantigens for CD8+ T cells, as we found that these Qa-1b-restricted T cells dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background, or type of processing deficiency, was recognized by this T cell subset, complying with the conserved nature of Qa-1b. Target cell recognition depended on T cell receptor and Qa-1b interaction, and immunization with identified peptide epitopes demonstrated in vivo priming of CD8+ T cells. Our data reveal that Qa-1b, and most likely its human homologue human leukocyte antigen-E, is important for the defense against processing-deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8+ T cells. Show less
Oliveira, C.C.; Veelen, P.A. van; Querido, B.; Ru, A. de; Sluijter, M.; Laban, S.; ... ; Hall, T. van 2010
The nonclassical major histocompatibility complex (MHC) Qa-1(b) accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural... Show moreThe nonclassical major histocompatibility complex (MHC) Qa-1(b) accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, which are expressed by natural killer cells and CD8(+) T cells. We here describe that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen-processing pathway. This novel peptide repertoire represents immunogenic neoantigens for CD8(+) T cells, as we found that these Qa-1(b)-restricted T cells dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background, or type of processing deficiency, was recognized by this T cell subset, complying with the conserved nature of Qa-1(b). Target cell recognition depended on T cell receptor and Qa-1(b) interaction, and immunization with identified peptide epitopes demonstrated in vivo priming of CD8(+) T cells. Our data reveal that Qa-1(b), and most likely its human homologue human leukocyte antigen-E, is important for the defense against processing-deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8(+) T cells. Show less
