Disease relevance of H2-Q1

• Thus, this report increases the number of MHC class Ib antigen-presenting molecules known for Salmonella antigens to three: Qa-1, HLA-E, and now H2-M3 [1].
• Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes [2].

High impact information on H2-Q1

• Both Ld and Qsm can interact with Qa-1 to form cell surface-expressed heterodimers in vivo [3].
• These interactions may enable increased levels of Qa-1 to reach the cell surface and may subsequently influence T cell recognition of Qa-1 and/or Ld molecules [3].
• Furthers analyses of a panel of recombinants revealed that the 50-kD protein coprecipitated with Qa-1 in H-2b haplotype mouse strains is encoded or controlled by a gene centromeric to major histocompatibility complex class II I-E beta [3].
• These Qa-1 heterodimers are not expressed in H-2k haplotype cells [3].
• The class I-b molecule Qa-1 forms heterodimers with H-2Ld and a novel 50-kD glycoprotein encoded centromeric to I-E beta [3].

Biological context of H2-Q1

• The class I gene RT1.46 (l) has an open reading frame, but it is unlike H2-D due to a unique 5'UTR shared with H2-Q1 and Q2, the absence of the B2 SINE repeat characteristic of H2-D/L, and the apparent lack of surface expression [4].
• Restriction maps of overlapping lambda and cosmid clones reveal that there are only five Qak genes: Q1k, Q2k, Q4k, Q10k and a Q5/9 hybrid, presumably generated by unequal homologous recombination [5].
• TCDD-induced down-regulation of MHC Q1b requires both the aromatic hydrocarbon receptor and the aromatic hydrocarbon receptor nuclear translocator, transcription factors that up-regulate other genes in response to TCDD [6].
• Each of the four common Qa-1 phenotypes was shown to exhibit unique antigenic determinants [7].
• The nature of cell surface determinants detected by Qa-1-specific alloantisera and cytotoxic T lymphocytes (CTL) in mice of the H-2f, Qa-1d genotype was investigated [8].

Anatomical context of H2-Q1

• Clonal analysis of the anti-Qa-1 cytotoxic T lymphocyte repertoire: definition of the Qa-1d and Qa-1c alloantigens and cross-reactivity with H-2 [7].
• Analysis of Qa-1 isolated from detergent lysates of surface labeled cells indicated this molecule was a slightly acidic 48,000 to 50,000 dalton glycoprotein that displayed little charge heterogeneity on resting lymphocytes [9].
• Listeria-infected bone marrow macrophages from congenic and recombinant strains of mice were lysed only when they shared the H2-T region or were Qa1-compatible with the immune cytotoxic cells; sharing of the H2-D, Q, or M region was insufficient [10].
• Cytotoxic T lymphocytes (CTL) activated in H-2 identical, Qa-1 disparate mixed leukocyte cultures recognize H-2-nonrestricted target antigens indistinguishable by strain or tissue distribution from serologically defined Qa-1 antigens [11].
• Fetal NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between wild-type and class I-deficient blasts but, surprisingly, distinguish efficiently between certain wild-type and class I-deficient tumor cells [12].

Associations of H2-Q1 with chemical compounds

• Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used to examine and compare the products of the Qa-1 locus [9].
• Down-regulation of major histocompatibility complex Q1b gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin [6].
• Whereas mouse L cells and human C1R cells transfected with Qa1 were resistant to lysis by these effectors, Qa1-transfected TAP-deficient human T2 cells showed no resistance despite expressing high levels of surface Qa1 [13].

Other interactions of H2-Q1

• The Qa-1/Ld and Qa-1/Qsm heterodimers are associated by noncovalent interactions and occur only between fully processed proteins [3].
• One exhibited highest similarity to an H2 class I b gene, H2-T23 (encoding the Qa1 antigen) [14].
• In the present study we describe an in vivo model of antigen-specific transplantation tolerance to skin allografts using mice congenic at Qa1, a ubiquitously expressed class I-like molecule encoded to the right of H-2D [15].
• The Qed-1 locus was mapped distal to Qa-2 [16].
• One of the Pema class I cDNA clones classified as H2-K, D/L-like (class I a) is predicted to encode an identical peptide, implying that an antigen binding protein (Qa1) and the antigen to which it binds (the product of Qdm) has been conserved for over 50 My [14].

Analytical, diagnostic and therapeutic context of H2-Q1

• A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions [17].
• Peptide mapping analysis also demonstrated that the Tlaa and Qa-1a allelic products were distinct from one another, as well as being very different from the other three Qa-1 allelic products [9].
• Expression of Qa-1 protein was assessed on ocular frozen tissue sections by immunohistochemistry, and within aqueous humor by western blotting [18].

References