CD1d1 Mutant Mice Are Deficient in Natural T Cells That PromptlyProduce IL-4

The H-2 histocompatibility complex of the mouse is a multigene family, some members of which are essential for the immune response to foreign antigens. The structure and organization of these genes have been established by molecular cloning, and their regulation and function is being defined by expression of the cloned genes.

https://science.sciencemag.org/content/sci/233/4762/437.full.pdf

Molecular biology of the H-2 histocompatibility complex

The TL region of the major histocompatibility complex of the mouse contains dozens of tandemly arranged class I genes, including those encoding the thymus leukemia (TL) antigens. TL antigens have been thought to be expressed only on the surface of some T lineage cells, namely immature thymocytes of some mouse strains (TL+ strains), some leukemia cells, and activated T cells. While the function of TL antigens is unknown, recent studies have implicated the products of at least some TL region class I genes as molecules that present antigens to gamma/delta T cells. Since some gamma/delta T cells are known to be specifically associated with certain epithelial tissues, we have investigated the expression of some TL region class I genes in a variety of epithelium-containing tissues. Our results show that the TL antigen gene of C57BL/6 mice, T3b, and the TL antigen genes of BALB/c mice, T3d (previously T3c) and T18d (previously T13c), are highly expressed in the epithelium of the small intestine. In the case of T3b, we further show, using a T3 product-specific antibody, that its product is expressed on the surface of the columnar epithelial cells. In addition, we demonstrated that two other TL region class I genes of C57BL/6 origin, T9b and T21b, are also expressed nearly exclusively in intestinal epithelial cells. These results are consistent with the hypothesis that the products of these TL region class I genes are recognized by gamma/delta T cell receptors of intestinal intraepithelial lymphocytes, a subset of gamma/delta T cells that is localized in the intestinal epithelium and has a restricted V gamma repertoire. Finally, our study indicates that the relative levels of expression of the two homologous TL antigen genes, T3d and T18d, differ widely between the thymus and the intestine.

https://rupress.org/jem/article-pdf/174/1/213/1101597/213.pdf

Highly restricted expression of the thymus leukemia antigens on intestinal epithelial cells.

https://www.cell.com/immunity/pdf/S1074-7613(03)00027-X.pdf

The Crystal Structure of a TL/CD8αα Complex at 2.1 Å Resolution: Implications for Modulation of T Cell Activation and Memory

The polymerase chain reaction was used to isolate clones with class I major histocompatibility complex sequences from fish (carp), amphibian (axolotl), and two species of reptile (lizard and snake). The lizard and snake clones were used to isolate class I cDNA clones. All the sequence showed the expected evolutionary relatedness. The carp and axolotl clones and one lizard cDNA clone lacked the first systeine in the α3 domain which in other class I heavy chains forms an intradomain disulfide bond. A small number of amino acid residues are conserved in the class I heavy chain sequences from all five classes of vertebrates. In the first two domains they are symmetrically clustered and contribute to intra-and interdomain contacts. None of these invariant residues are at peptide-binding, T-cell receptor-interacting, or CD8-binding positions.

Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure.

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. In order to study the fine structure and interrelationships of genes of the Tla subregion, a Tla-specific probe was isolated from the TL-encoding T13c gene of BALB/c mice (Tlac haplotype). The probe hybridized with two Tla genes in the Tlac haplotype (T13c and T3c) and with only one in the Tlab haplotype (T3b). 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. The T3b gene, while not transcribed in the tissues of the TL- strain C57BL6, was shown to be transcriptionally active in the TL-expressing leukemic cell line ERLD derived from that strain. The T3b gene was cloned and its complete DNA sequence was determined. These data permit complete comparison of two Tla-region genes, T3b and its homologue T13c, and allow us to conclude that these genes show extraordinarily high sequence conservation, in contrast to alleles of the H-2K- and H-2D-region genes. Comparison of T3b with other class I sequences in the H-2 and Qa subregions suggests that the T3-subset genes are the most divergent from other class I genes.

Conservation and diversity in the class I genes of the major histocompatibility complex: sequence analysis of a Tlab gene and comparison with a Tlac gene

Thethymus leukemia (TL)antigens, encoded byclass Igenes intheTlasubregion ofthemajorhistocom- patibility complex (MHC), arecell surface molecules expressed onthymocytes ofcertain strains ofmiceandoncertain T-cell leukemias. Inorder tostudy thefine structure andinterrela- tionships ofgenes oftheTMsubregion, aTla-specific probe was isolated fromtheTL-encoding T13C gene ofBALB/cmice(Tb" haplotype). Theprobe hybridized with twoTlagenes intheThf haplotype (T13C andT3C) andwithonlyoneintheTlab haplotype (T3b). Examination ofthis subset ofTlagenes (T3b, T3Y, andT13c) byrestriction enzyme analysis andoligonucle- otide hybridization studies confirmed thatT3bistheallele of T3Candthat T3YandT13c mayhavearisen byduplication. The T3bgene, while nottranscribed inthetissues oftheTL-strain C57BL6, wasshowntobetranscriptionall y active inthe TL-expressing leukemic cell line ERLDderived fromthat strain. TheT3b genewascloned andits complete DNAsequence wasdetermined. Thesedatapermit complete comparison of twoTla-region genes, T3b andits homologue T13c, andallow us toconclude thatthese genes showextraordinarily highse- quence conservation, incontrast toalleles oftheH-2K-and H-2D-region genes. Comparison ofT3bwithother class I sequences intheH-2andQasubregions suggests thatthe T3-subset genes arethemostdivergent fromother class Igenes.

Conservation anddiversity intheclass Igenesofthemajor histocompatibili ty complex: Sequence analysis ofa Tiab geneandcomparison withaTlac gene (multigene family/thymus leukemia antigen/DNA sequence)

P. A. Pontarotti

Papers

Conservation and diversity in the class I genes of the major histocompatibility complex: sequence analysis of a Tlab gene and comparison with a Tlac gene

Conservation anddiversity intheclass Igenesofthemajor histocompatibili ty complex: Sequence analysis ofa Tiab geneandcomparison withaTlac gene (multigene family/thymus leukemia antigen/DNA sequence)