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

Wu, Michael; Kaer, Luc Van; Itohara, Shigeyoshi; Tonegawa, Susumu

doi:10.1084/jem.174.1.213

Cited by 108 publications

(58 citation statements)

References 35 publications

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“…Class Ib MHC genes Q1 (29,30), Q2 (29,31), T3 (32,33), and unexpectedly H2-Bl were found to be transcribed predominantly in the gastrointestinal tract ( Fig. 1, top panel).…”

Section: Intestinal Tissues Of C57bl/6j Mice Transcribe Multiple Clasmentioning

confidence: 99%

The Murine Family of Gut-Restricted Class Ib MHC Includes Alternatively Spliced Isoforms of the Proposed HLA-G Homolog, “Blastocyst MHC”

Guidry

Stroynowski

2005

The Journal of Immunology

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The gastrointestinal tract is populated by a multitude of specialized immune cells endowed with receptors for classical (class Ia) and nonclassical (class Ib) MHC proteins. To identify class I products that engage these receptors and impact immunity/tolerance, we studied gut-transcribed class Ib loci and their polymorphism in inbred, outbred, and wild-derived mice. Intestinal tissues enriched in epithelial cells contained abundant transcripts of ubiquitously expressed and preferentially gut-restricted Q and T class I loci. The latter category included the “blastocyst Mhc” gene, H2-Bl, and its putative paralog, Tw5. Expression of H2-Bl was previously detected only at the maternal/fetal interface, where it was proposed to induce immune tolerance via interactions with CD94/NKG2A receptors. Analysis of coding region polymorphism performed here revealed two major alleles of H2-Bl with conserved residues at positions critical for class I protein folding and peptide binding. Both divergent alleles are maintained in outbred and wild mice under selection for fecundity and pathogen resistance. Surprisingly, we found that alternative splicing of H2-Bl mRNA in gut tissues is prevalent and allele-specific. It leads to strain-dependent expression of diverse repertoires of canonical and noncanonical transcripts that may give rise to distinct ligands for intestinal NK cell, T cell, and/or intraepithelial lymphocyte receptors.

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“…Class Ib MHC genes Q1 (29,30), Q2 (29,31), T3 (32,33), and unexpectedly H2-Bl were found to be transcribed predominantly in the gastrointestinal tract ( Fig. 1, top panel).…”

Section: Intestinal Tissues Of C57bl/6j Mice Transcribe Multiple Clasmentioning

confidence: 99%

The Murine Family of Gut-Restricted Class Ib MHC Includes Alternatively Spliced Isoforms of the Proposed HLA-G Homolog, “Blastocyst MHC”

Guidry

Stroynowski

2005

The Journal of Immunology

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“…TL is highly expressed on immature thymocytes in some strains of mice but not others. It is expressed on epithelial cells in the small intestine of all strains (3,4), suggesting that this nonclassical class I molecule may play a specialized role in mucosal immunity. The TL gene products are closely related, with Ͼ95% sequence similarity and there is evidence for evolutionary selection in mice to maintain conservation in the ␣1 and ␣2 domains of these molecules (5).…”

mentioning

confidence: 99%

Peptide-Independent Folding and CD8αα Binding by the Nonclassical Class I Molecule, Thymic Leukemia Antigen

Weber¹,

Attinger

Kemball³

et al. 2002

The Journal of Immunology

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The nonclassical class I molecule, thymic leukemia (TL), has been shown to be expressed on intestinal epithelial cells and to interact with CD8+ intraepithelial T lymphocytes. We generated recombinant soluble TL (T18d) H chains in bacteria as inclusion bodies and refolded them with β2-microglobulin in the presence or absence of a random peptide library. Using a mAb, HD168, that recognizes a conformational epitope on native TL molecules, we observed that protein folds efficiently in the absence of peptide. Circular dichroism analysis demonstrated that TL molecules have structural features similar to classical class I molecules. Moreover, thermal denaturation experiments indicated that the melting temperature for peptide-free TL is similar to values reported previously for conventional class I-peptide complexes. Our results also show that CD8αα binding is not dependent on either TL-associated peptide or TL glycosylation.

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“…In normal mice, the expression of TL is restricted to the intestines in all mouse strains, but also the thymus of TL + strains ( Fig. 1), 1,14,15) suggesting that TL plays a specialized role(s) in these organs, especially in the intestines. TL was originally described in 1963 as a serologically defined tumor-specific antigen, [16][17][18] since a proportion of T lymphomas/leukemias originating even from TL -strains (which do not express TL in the thymus) express TL (Fig.…”

mentioning

confidence: 99%

Thymus‐leukemia antigen (TL) as a major histocompatibility complex (MHC) class Ib molecule and tumor‐specific antigen

Tsujimura¹,

Obata

Takahashi

2004

Cancer Science

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Mouse thymus-leukemia antigens (TL) belong to the family of major histocompatibility complex (MHC) class Ib antigens and have a unique mode of expression, i.e., in contrast to other MHC class Ib or Ia antigens, they are found restricted to the intestines in all mouse strains, but also in the thymus of certain strains (TL + strains). Nevertheless, a proportion of T lymphomas/leukemias in strains that do not express TL in the thymus (TL -strains) feature TL as a tumor antigen. TL was originally defined serologically, but subsequently we have succeeded in generating T cell receptor (TCR) α α α αβ β β β and γ γ γ γδ δ δ δ cytotoxic T lymphocytes (CTL) recognizing TL. By use of TL tetramers free from peptides and transfectants expressing various TL/H-2 chimeric molecules, we have been able to show that TL-specific CTL recognize the α α α α1/ α α α α2 domain of TL without any additional antigen molecules. We previously reported that one of TL's functions in the thymus is positive selection of TCRγ γ γ γδ δ δ δ CTL. Recent studies with TL tetramers revealed that they can bind to normal intestinal intraepithelial lymphocytes (iIEL) and thymocytes in a CD8-dependent, but TCR/CD3-independent manner, while their binding to TL-specific CTL is TCR/CD3-and CD8-dependent. The possible significance of these findings in relation to the roles of TL in the intestines is discussed. ouse thymus-leukemia antigens (TL) are major histocompatibility complex (MHC) class Ib (or nonclassical MHC class I) molecules encoded by closely related genes in the T region of mouse MHC. 1-5) TL genes have overall structures similar to MHC class Ia (classical MHC class I) genes, and show high homology among themselves, but they are only distantly related to other MHC class Ia and Ib genes, indicating the operation of natural selection to preserve the function of TL. 6)The products of TL genes are glycoproteins with molecular weights of approximately 45,000 daltons [7][8][9] and are expressed on the cell surface with β 2 -microglobulin (β 2 M), but they can be independently expressed transporters associated with antigen processing (TAP). 4,[10][11][12] A recent crystallographical analysis yielded the important finding that T18 d -TL has no antigen-binding groove wide enough to accommodate a peptide or lipid antigen, 13) in contrast to other MHC class Ia and Ib products. In normal mice, the expression of TL is restricted to the intestines in all mouse strains, but also the thymus of TL + strains (Fig. 1), 1,14,15) suggesting that TL plays a specialized role(s) in these organs, especially in the intestines. TL was originally described in 1963 as a serologically defined tumor-specific antigen, [16][17][18] since a proportion of T lymphomas/leukemias originating even from TL -strains (which do not express TL in the thymus) express TL (Fig. 1). We recently demonstrated that TL can also serve as a transplantation and tumor rejection antigen for T cells 19,20) and that both T cell receptor (TCR) αβ and γδ cytotoxic T lymphocytes (CTL) specific for TL can kill...

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

Cited by 108 publications

References 35 publications

The Murine Family of Gut-Restricted Class Ib MHC Includes Alternatively Spliced Isoforms of the Proposed HLA-G Homolog, “Blastocyst MHC”

The Murine Family of Gut-Restricted Class Ib MHC Includes Alternatively Spliced Isoforms of the Proposed HLA-G Homolog, “Blastocyst MHC”

Peptide-Independent Folding and CD8αα Binding by the Nonclassical Class I Molecule, Thymic Leukemia Antigen

Thymus‐leukemia antigen (TL) as a major histocompatibility complex (MHC) class Ib molecule and tumor‐specific antigen

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