Abstract
Enhanced major histocompatibility complex (MHC) class I expression is a prominent early feature of pancreatic beta-cell pathology in autoimmune diabetes. The number and nature of class I MHC loci expressed by beta cells are generally undefined and potentially critical to the onset and progression of insulitis. Mounting evidence indicates that the non-classical MHC class IB molecule Qa-1, encoded by H2-T23, is capable of presenting antigens to alpha beta and gamma delta T cells and that lymphocytes restricted to Qa-1 may contribute immunoregulatory functions. We compared the expression of Qa-1 and MHC class IA in a beta-cell line (beta TC6-F7) before and after treatment with the insulitic cytokine interferon-gamma (IFN-gamma). Similar to MHC class IA, Qa-1 was expressed constitutively at a low level in beta TC6-F7 cells, with both T23b mRNA and cell surface Qa-1b being up-regulated following 24-hr treatment with mouse IFN-gamma. Based on binding characteristics established for the predominant Qa-1-binding peptide, Qa-1 determinant modifier (Qdm), we also examined the possibility that Qa-1 binding peptides may be encoded in the preproinsulin leader sequence. One nonarmeric peptide (Ins II: ALWMRFLPL) derived from the preproinsulin II leader sequence was recognized by a Qa-1b-specific cytotoxic T-lymphocyte (CTL) clone. Specific binding of Ins II to Qa-1b was confirmed by a CTL peptide-blocking assay. Demonstration of IFN-gamma-regulated Qa-1 expression in beta cells and identification of a Qa-1-binding peptide in the preproinsulin leader sequence invoke further consideration of possible roles of Qa-1 in the progression of islet inflammation.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aldrich C. J., DeCloux A., Woods A. S., Cotter R. J., Soloski M. J., Forman J. Identification of a Tap-dependent leader peptide recognized by alloreactive T cells specific for a class Ib antigen. Cell. 1994 Nov 18;79(4):649–658. doi: 10.1016/0092-8674(94)90550-9. [DOI] [PubMed] [Google Scholar]
- Aldrich C. J., Jenkins R. N., Rich R. R. 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. J Immunol. 1986 Jan;136(2):383–388. [PubMed] [Google Scholar]
- Aldrich C. J., Rodgers J. R., Rich R. R. Regulation of Qa-1 expression and determinant modification by an H-2D-linked gene, Qdm. Immunogenetics. 1988;28(5):334–344. doi: 10.1007/BF00364232. [DOI] [PubMed] [Google Scholar]
- Aldrich C. J., Waltrip R., Hermel E., Attaya M., Lindahl K. F., Monaco J. J., Forman J. T cell recognition of QA-1b antigens on cells lacking a functional Tap-2 transporter. J Immunol. 1992 Dec 15;149(12):3773–3777. [PubMed] [Google Scholar]
- André I., Gonzalez A., Wang B., Katz J., Benoist C., Mathis D. Checkpoints in the progression of autoimmune disease: lessons from diabetes models. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2260–2263. doi: 10.1073/pnas.93.6.2260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bach J. F. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev. 1994 Aug;15(4):516–542. doi: 10.1210/edrv-15-4-516. [DOI] [PubMed] [Google Scholar]
- Castaño L., Eisenbarth G. S. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol. 1990;8:647–679. doi: 10.1146/annurev.iy.08.040190.003243. [DOI] [PubMed] [Google Scholar]
- Cauley L. S., Cauley K. A., Shub F., Huston G., Swain S. L. Transferable anergy: superantigen treatment induces CD4+ T cell tolerance that is reversible and requires CD4-CD8- cells and interferon gamma. J Exp Med. 1997 Jul 7;186(1):71–81. doi: 10.1084/jem.186.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Connolly D. J., Cotterill L. A., Hederer R. A., Thorpe C. J., Travers P. J., McVey J. H., Dyson J., Robinson P. J. A cDNA clone encoding the mouse Qa-1a histocompatibility antigen and proposed structure of the putative peptide binding site. J Immunol. 1993 Dec 1;151(11):6089–6098. [PubMed] [Google Scholar]
- D'Ambra R., Surana M., Efrat S., Starr R. G., Fleischer N. Regulation of insulin secretion from beta-cell lines derived from transgenic mice insulinomas resembles that of normal beta-cells. Endocrinology. 1990 Jun;126(6):2815–2822. doi: 10.1210/endo-126-6-2815. [DOI] [PubMed] [Google Scholar]
- DeCloux A., Woods A. S., Cotter R. J., Soloski M. J., Forman J. Dominance of a single peptide bound to the class I(B) molecule, Qa-1b. J Immunol. 1997 Mar 1;158(5):2183–2191. [PubMed] [Google Scholar]
- Eardley D. D., Hugenberger J., McVay-Boudreau L., Shen F. W., Gershon R. K., Cantor H. Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. J Exp Med. 1978 Apr 1;147(4):1106–1115. doi: 10.1084/jem.147.4.1106. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flaherty L., Elliott E., Tine J. A., Walsh A. C., Waters J. B. Immunogenetics of the Q and TL regions of the mouse. Crit Rev Immunol. 1990;10(2):131–175. [PubMed] [Google Scholar]
- Harrison L. C., Campbell I. L., Allison J., Miller J. F. MHC molecules and beta-cell destruction. Immune and nonimmune mechanisms. Diabetes. 1989 Jul;38(7):815–818. doi: 10.2337/diab.38.7.815. [DOI] [PubMed] [Google Scholar]
- Imani F., Soloski M. J. Heat shock proteins can regulate expression of the Tla region-encoded class Ib molecule Qa-1. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10475–10479. doi: 10.1073/pnas.88.23.10475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jiang H., Ware R., Stall A., Flaherty L., Chess L., Pernis B. Murine CD8+ T cells that specifically delete autologous CD4+ T cells expressing V beta 8 TCR: a role of the Qa-1 molecule. Immunity. 1995 Feb;2(2):185–194. doi: 10.1016/s1074-7613(95)80079-4. [DOI] [PubMed] [Google Scholar]
- Knaack D., Fiore D. M., Surana M., Leiser M., Laurance M., Fusco-DeMane D., Hegre O. D., Fleischer N., Efrat S. Clonal insulinoma cell line that stably maintains correct glucose responsiveness. Diabetes. 1994 Dec;43(12):1413–1417. doi: 10.2337/diab.43.12.1413. [DOI] [PubMed] [Google Scholar]
- Kurepa Z., Forman J. Peptide binding to the class Ib molecule, Qa-1b. J Immunol. 1997 Apr 1;158(7):3244–3251. [PubMed] [Google Scholar]
- Kurlander R. J., Shawar S. M., Brown M. L., Rich R. R. Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses. Science. 1992 Jul 31;257(5070):678–679. doi: 10.1126/science.1496381. [DOI] [PubMed] [Google Scholar]
- Liu Q., Arkins S., Biragyn A., Minshall C., Parnet P., Dantzer R., Kelley K. W. Competitive reverse transcriptase-polymerase chain reaction using a synthetic internal RNA standard to quantitate transcripts for leukocyte-derived hormones. Neuroimmunomodulation. 1994 Jan;1(1):33–41. doi: 10.1159/000097088. [DOI] [PubMed] [Google Scholar]
- Lowen L. C., Aldrich C. J., Forman J. Analysis of T cell receptors specific for recognition of class IB antigens. J Immunol. 1993 Dec 1;151(11):6155–6165. [PubMed] [Google Scholar]
- Rabinovitch A., Suarez-Pinzon W. L., Sorensen O., Bleackley R. C., Power R. F. IFN-gamma gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice. J Immunol. 1995 May 1;154(9):4874–4882. [PubMed] [Google Scholar]
- Rabinovitch A., Suarez-Pinzon W. L., Sorensen O., Bleackley R. C., Power R. F. IFN-gamma gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice. J Immunol. 1995 May 1;154(9):4874–4882. [PubMed] [Google Scholar]
- Sharma P., Joyce S., Chorney K. A., Griffith J. W., Bonneau R. H., Wilson F. D., Johnson C. A., Flavell R. A., Chorney M. J. Thymus-leukemia antigen interacts with T cells and self-peptides. J Immunol. 1996 Feb 1;156(3):987–996. [PubMed] [Google Scholar]
- Shawar S. M., Vyas J. M., Rodgers J. R., Rich R. R. Antigen presentation by major histocompatibility complex class I-B molecules. Annu Rev Immunol. 1994;12:839–880. doi: 10.1146/annurev.iy.12.040194.004203. [DOI] [PubMed] [Google Scholar]
- Sieling P. A., Chatterjee D., Porcelli S. A., Prigozy T. I., Mazzaccaro R. J., Soriano T., Bloom B. R., Brenner M. B., Kronenberg M., Brennan P. J. CD1-restricted T cell recognition of microbial lipoglycan antigens. Science. 1995 Jul 14;269(5221):227–230. doi: 10.1126/science.7542404. [DOI] [PubMed] [Google Scholar]
- Soloski M. J., DeCloux A., Aldrich C. J., Forman J. Structural and functional characteristics of the class IB molecule, Qa-1. Immunol Rev. 1995 Oct;147:67–89. doi: 10.1111/j.1600-065x.1995.tb00088.x. [DOI] [PubMed] [Google Scholar]
- Springer T., Galfre G., Secher D., Milstein C. Monoclonal xenogeneic antibodies to mouse leukocyte antigens: identification of macrophage-specific and other differentiation antigens. Curr Top Microbiol Immunol. 1978;81:45–50. doi: 10.1007/978-3-642-67448-8_7. [DOI] [PubMed] [Google Scholar]
- Stroynowski I. Molecules related to class-I major histocompatibility complex antigens. Annu Rev Immunol. 1990;8:501–530. doi: 10.1146/annurev.iy.08.040190.002441. [DOI] [PubMed] [Google Scholar]
- Transy C., Nash S. R., David-Watine B., Cochet M., Hunt S. W., 3rd, Hood L. E., Kourilsky P. A low polymorphic mouse H-2 class I gene from the Tla complex is expressed in a broad variety of cell types. J Exp Med. 1987 Aug 1;166(2):341–361. doi: 10.1084/jem.166.2.341. [DOI] [PMC free article] [PubMed] [Google Scholar]