Disease relevance of H2-T18

• The thymus leukemia (TL) antigens, encoded by class I genes in the Tla subregion of the major histocompatibility complex (MHC), are cell surface molecules expressed on thymocytes of certain strains of mice and on certain T-cell leukemias [1].
• Embryonal carcinoma cells express Qa and Tla class I genes of the major histocompatibility complex [2].
• Qa or Tla haplotypes did not appear to influence demyelination [3].
• The Qa and Tla genes did not appear to be critical in determining susceptibility to the encephalitis [4].

High impact information on H2-T18

• M3 is as divergent from classical, antigen-presenting H-2 molecules as from other class I genes of the Hmt and the Qa/Tla regions [5].
• The H-2, Qa, and Tla genes of the murine major histocompatibility complex are related to each other by DNA sequence homology [6].
• Linked to the murine MHC are genes encoding the class I-like Qa and Tla antigens, which are closely related structurally to H-2K, D and L, as they are also 45,000-Mr cell surface glycoproteins associated with beta 2-microglobulin [7].
• A cDNA clone corresponding to a mRNA present at elevated levels in transformed fibroblasts encodes a Qa/Tla class I major histocompatibility complex (MHC) antigen [8].
• Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice [9].

Biological context of H2-T18

• Using Southern blot hybridization on the DNAs of different inbred mouse strains, we mapped the pseudogene to the Qa-2,3 region, a part of the Tla complex on chromosome 17 that is adjacent to the major histocompatibility complex [10].
• The probe hybridized with two Tla genes in the Tlac haplotype (T13c and T3c) and with only one in the Tlab haplotype (T3b) [1].
• The TSEs exist as submegabase-long clusters of tandem repeats localized in the Tla region of the major histocompatibility complex of all t haplotype chromosomes examined [11].
• Submegabase clusters of unstable tandem repeats unique to the Tla region of mouse t haplotypes [11].
• We have determined the DNA sequence of a gene encoding a thymus leukemia (TL) antigen in the BALB/c mouse, and have more definitively mapped the cloned BALB/c Tla-region class I gene clusters [12].

Anatomical context of H2-T18

• Qat-4 and Qat-5, new murine T-cell antigens governed by the Tla region and identified by monoclonal antibodies [13].
• A panel of peritoneal exudate cells (PEC) from mice bearing nonrecombinant and recombinant H-2-Tla haplotypes and their F1 hybrids was used as the source of target and inhibitor cells for direct lytic and competitive inhibition assays [14].
• Mutant classical class I molecules substituted with TL Ag amino acids at these positions mimic the ability to interact with CD8alphaalpha and modulate lymphocyte function [15].
• We conclude from these data that, in the cell membrane of thymocytes, virtually all the beta2m molecules are associated with H-2 and Tla, but not with Thy-1, and that on the cell surface of T or B lymphocytes, virtually all beta2m is associated with H-2 but not with Ia [16].
• Antigens specified by the Tla locus are expressed on the surface of murine Langerhans cells [17].

Associations of H2-T18 with chemical compounds

• Peanut agglutinin-positive thymocytes, peanut agglutinin-negative thymocytes, cortisone-resistant thymocytes, and unfractionated thymocytes were prepared from congeneic C57BL/6 Tla mice [18].
• Three Tla region-specific probes have been generated from the BALB/c genomic cosmid clone C6 [19].
• Serum from mice of a congenic strain being derived in our laboratory, which differs from B6 at two unlinked loci, Tla and nu, exhibited similar reactivity against the B6-H-2k LPS-stimulated lymphoblasts, implying that a competent T cell compartment is not necessary for generation of this reactivity [20].

Physical interactions of H2-T18

• We include into the H-2 complex the cluster of Qa and Tla loci, which we consider as class I loci (Klein et al. 1983) [21].

Other interactions of H2-T18

• Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene [22].
• Northern (RNA) blot hybridizations, polymerase chain reaction studies, and cDNA cloning experiments demonstrate that EC lines transcribe genes allelic to the Tla region gene "37", Qa-2 region gene "Q7", and another, previously uncharacterized, class I-like gene [2].
• Tests with recombinant inbred strains and with H-3 congenic strains show that, in addition to the Tla region, a gene linked to or identical with the beta 2-microglobulin-b-allele is required for the expression of Qa-11 as well [23].
• However, unlike the classical class I genes, the Thy19.4 gene maps approximately 1 cm distal to the Tla region of the MHC, in the same region as the gene encoding the Hmt element of the maternally transmitted antigen [24].
• At least one new TL antigen is defined (TL.7), and at least one more Tla allele, bringing the total number of known Tla alleles to six [25].

Analytical, diagnostic and therapeutic context of H2-T18

• Accordingly, we may have isolate genes encoding lymphoid differentiation antigens of the Tla complex as well as those encoding transplantation antigens among the 30 to 40 different genomic clones isolated from our sperm library [10].
• Examination of this subset of Tla genes (T3b, T3c, and T13c) by restriction enzyme analysis and oligonucleotide hybridization studies confirmed that T3b is the allele of T3c and that T3c and T13c may have arisen by duplication [1].
• Multiple species of TL mRNA were detected in TL+ cells by Northern blot analysis with pTL1, and different Tla haplotypes could be distinguished on the basis of characteristic patterns of TL mRNA [26].
• Molecular relationships between beta2m and other cell surface antigens (H-2, Tla, Ia, and Thy-1) were studied with the double immunofluorescence method [16].
• Cell surface forms of TL were detectable by immunoprecipitation on activated peripheral T cells from Tla haplotypes except Tla(b), in agreement with expression observed on thymocytes [27].

References