Abstract
Rather unexpectedly, major histocompatibility complex class II- deficient mice have a significant population of peripheral CD4+ T lymphocytes. We have investigated these cells at the population and clonal levels. CD4+ T lymphocytes from class II-deficient animals are thymically derived, appear early in ontogeny, exhibit the phenotype of resting memory cells, are potentially functional by several criteria, and have a diverse T cell receptor repertoire. They do not include substantially elevated numbers of NK1.1+ cells. Hybridomas derived after polyclonal stimulation of the CD4+ lymphocytes from class II- deficient animals include a subset with an unusual reactivity pattern, responding to splenocytes from many mouse strains including the strain of origin. Most members of this subset recognize the major histocompatibility complex class Ib molecule CD1; their heterogeneous reactivities and T cell receptor usage further suggest the involvement of peptides and/or highly variable posttranslational modifications.
Full Text
The Full Text of this article is available as a PDF (1.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- Arase H., Arase N., Nakagawa K., Good R. A., Onoé K. NK1.1+ CD4+ CD8- thymocytes with specific lymphokine secretion. Eur J Immunol. 1993 Jan;23(1):307–310. doi: 10.1002/eji.1830230151. [DOI] [PubMed] [Google Scholar]
- Balk S. P., Bleicher P. A., Terhorst C. Isolation and expression of cDNA encoding the murine homologues of CD1. J Immunol. 1991 Jan 15;146(2):768–774. [PubMed] [Google Scholar]
- Balk S. P., Burke S., Polischuk J. E., Frantz M. E., Yang L., Porcelli S., Colgan S. P., Blumberg R. S. Beta 2-microglobulin-independent MHC class Ib molecule expressed by human intestinal epithelium. Science. 1994 Jul 8;265(5169):259–262. doi: 10.1126/science.7517575. [DOI] [PubMed] [Google Scholar]
- Balk S. P., Ebert E. C., Blumenthal R. L., McDermott F. V., Wucherpfennig K. W., Landau S. B., Blumberg R. S. Oligoclonal expansion and CD1 recognition by human intestinal intraepithelial lymphocytes. Science. 1991 Sep 20;253(5026):1411–1415. doi: 10.1126/science.1716785. [DOI] [PubMed] [Google Scholar]
- Ballas Z. K., Rasmussen W. NK1.1+ thymocytes. Adult murine CD4-, CD8- thymocytes contain an NK1.1+, CD3+, CD5hi, CD44hi, TCR-V beta 8+ subset. J Immunol. 1990 Aug 15;145(4):1039–1045. [PubMed] [Google Scholar]
- Beckman E. M., Porcelli S. A., Morita C. T., Behar S. M., Furlong S. T., Brenner M. B. Recognition of a lipid antigen by CD1-restricted alpha beta+ T cells. Nature. 1994 Dec 15;372(6507):691–694. doi: 10.1038/372691a0. [DOI] [PubMed] [Google Scholar]
- Bendelac A., Killeen N., Littman D. R., Schwartz R. H. A subset of CD4+ thymocytes selected by MHC class I molecules. Science. 1994 Mar 25;263(5154):1774–1778. doi: 10.1126/science.7907820. [DOI] [PubMed] [Google Scholar]
- Bendelac A., Matzinger P., Seder R. A., Paul W. E., Schwartz R. H. Activation events during thymic selection. J Exp Med. 1992 Mar 1;175(3):731–742. doi: 10.1084/jem.175.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bill J., Kanagawa O., Linten J., Utsunomiya Y., Palmer E. Class I and class II MHC gene products differentially affect the fate of V beta 5 bearing thymocytes. J Mol Cell Immunol. 1990;4(5):269–280. [PubMed] [Google Scholar]
- Bix M., Coles M., Raulet D. Positive selection of V beta 8+ CD4-8- thymocytes by class I molecules expressed by hematopoietic cells. J Exp Med. 1993 Sep 1;178(3):901–908. doi: 10.1084/jem.178.3.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bottomly K., Luqman M., Greenbaum L., Carding S., West J., Pasqualini T., Murphy D. B. A monoclonal antibody to murine CD45R distinguishes CD4 T cell populations that produce different cytokines. Eur J Immunol. 1989 Apr;19(4):617–623. doi: 10.1002/eji.1830190407. [DOI] [PubMed] [Google Scholar]
- Bradbury A., Belt K. T., Neri T. M., Milstein C., Calabi F. Mouse CD1 is distinct from and co-exists with TL in the same thymus. EMBO J. 1988 Oct;7(10):3081–3086. doi: 10.1002/j.1460-2075.1988.tb03173.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradley L. M., Croft M., Swain S. L. T-cell memory: new perspectives. Immunol Today. 1993 May;14(5):197–199. doi: 10.1016/0167-5699(93)90161-D. [DOI] [PubMed] [Google Scholar]
- Budd R. C., Miescher G. C., Howe R. C., Lees R. K., Bron C., MacDonald H. R. Developmentally regulated expression of T cell receptor beta chain variable domains in immature thymocytes. J Exp Med. 1987 Aug 1;166(2):577–582. doi: 10.1084/jem.166.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Calabi F., Jarvis J. M., Martin L., Milstein C. Two classes of CD1 genes. Eur J Immunol. 1989 Feb;19(2):285–292. doi: 10.1002/eji.1830190211. [DOI] [PubMed] [Google Scholar]
- Calabi F., Milstein C. A novel family of human major histocompatibility complex-related genes not mapping to chromosome 6. Nature. 1986 Oct 9;323(6088):540–543. doi: 10.1038/323540a0. [DOI] [PubMed] [Google Scholar]
- Candéias S., Katz J., Benoist C., Mathis D., Haskins K. Islet-specific T-cell clones from nonobese diabetic mice express heterogeneous T-cell receptors. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6167–6170. doi: 10.1073/pnas.88.14.6167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carayon P., Bord A. Identification of DNA-replicating lymphocyte subsets using a new method to label the bromo-deoxyuridine incorporated into the DNA. J Immunol Methods. 1992 Mar 4;147(2):225–230. doi: 10.1016/s0022-1759(12)80012-3. [DOI] [PubMed] [Google Scholar]
- Cochet M., Casrouge A., Dumont A. M., Transy C., Baleux F., Maloy W. L., Coligan J. E., Cazenave P. A., Kourilsky P. A new cell surface molecule closely related to mouse class I transplantation antigens. Eur J Immunol. 1989 Oct;19(10):1927–1931. doi: 10.1002/eji.1830191025. [DOI] [PubMed] [Google Scholar]
- Coles M. C., Raulet D. H. Class I dependence of the development of CD4+ CD8- NK1.1+ thymocytes. J Exp Med. 1994 Jul 1;180(1):395–399. doi: 10.1084/jem.180.1.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cosgrove D., Gray D., Dierich A., Kaufman J., Lemeur M., Benoist C., Mathis D. Mice lacking MHC class II molecules. Cell. 1991 Sep 6;66(5):1051–1066. doi: 10.1016/0092-8674(91)90448-8. [DOI] [PubMed] [Google Scholar]
- Dellabona P., Casorati G., Friedli B., Angman L., Sallusto F., Tunnacliffe A., Roosneek E., Lanzavecchia A. In vivo persistence of expanded clones specific for bacterial antigens within the human T cell receptor alpha/beta CD4-8- subset. J Exp Med. 1993 Jun 1;177(6):1763–1771. doi: 10.1084/jem.177.6.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Faure F., Jitsukawa S., Miossec C., Hercend T. CD1c as a target recognition structure for human T lymphocytes: analysis with peripheral blood gamma/delta cells. Eur J Immunol. 1990 Mar;20(3):703–706. doi: 10.1002/eji.1830200336. [DOI] [PubMed] [Google Scholar]
- Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
- Grusby M. J., Johnson R. S., Papaioannou V. E., Glimcher L. H. Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991 Sep 20;253(5026):1417–1420. doi: 10.1126/science.1910207. [DOI] [PubMed] [Google Scholar]
- Grégoire C., Rebaï N., Schweisguth F., Necker A., Mazza G., Auphan N., Millward A., Schmitt-Verhulst A. M., Malissen B. Engineered secreted T-cell receptor alpha beta heterodimers. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8077–8081. doi: 10.1073/pnas.88.18.8077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gückel B., Berek C., Lutz M., Altevogt P., Schirrmacher V., Kyewski B. A. Anti-CD2 antibodies induce T cell unresponsiveness in vivo. J Exp Med. 1991 Nov 1;174(5):957–967. doi: 10.1084/jem.174.5.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayakawa K., Lin B. T., Hardy R. R. Murine thymic CD4+ T cell subsets: a subset (Thy0) that secretes diverse cytokines and overexpresses the V beta 8 T cell receptor gene family. J Exp Med. 1992 Jul 1;176(1):269–274. doi: 10.1084/jem.176.1.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holcombe H. R., Castaño A. R., Cheroutre H., Teitell M., Maher J. K., Peterson P. A., Kronenberg M. Nonclassical behavior of the thymus leukemia antigen: peptide transporter-independent expression of a nonclassical class I molecule. J Exp Med. 1995 Apr 1;181(4):1433–1443. doi: 10.1084/jem.181.4.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ito K., Van Kaer L., Bonneville M., Hsu S., Murphy D. B., Tonegawa S. Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell. 1990 Aug 10;62(3):549–561. doi: 10.1016/0092-8674(90)90019-b. [DOI] [PubMed] [Google Scholar]
- Kitamura D., Roes J., Kühn R., Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991 Apr 4;350(6317):423–426. doi: 10.1038/350423a0. [DOI] [PubMed] [Google Scholar]
- Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
- Koo G. C., Peppard J. R. Establishment of monoclonal anti-Nk-1.1 antibody. Hybridoma. 1984 Fall;3(3):301–303. doi: 10.1089/hyb.1984.3.301. [DOI] [PubMed] [Google Scholar]
- Köntgen F., Süss G., Stewart C., Steinmetz M., Bluethmann H. Targeted disruption of the MHC class II Aa gene in C57BL/6 mice. Int Immunol. 1993 Aug;5(8):957–964. doi: 10.1093/intimm/5.8.957. [DOI] [PubMed] [Google Scholar]
- Lacasse J., Martin L. H. Detection of CD1 mRNA in Paneth cells of the mouse intestine by in situ hybridization. J Histochem Cytochem. 1992 Oct;40(10):1527–1534. doi: 10.1177/40.10.1382091. [DOI] [PubMed] [Google Scholar]
- Lantz O., Bendelac A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J Exp Med. 1994 Sep 1;180(3):1097–1106. doi: 10.1084/jem.180.3.1097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levitsky H. I., Golumbek P. T., Pardoll D. M. The fate of CD4-8- T cell receptor-alpha beta+ thymocytes. J Immunol. 1991 Feb 15;146(4):1113–1117. [PubMed] [Google Scholar]
- Necker A., Rebaï N., Matthes M., Jouvin-Marche E., Cazenave P. A., Swarnworawong P., Palmer E., MacDonald H. R., Malissen B. Monoclonal antibodies raised against engineered soluble mouse T cell receptors and specific for V alpha 8-, V beta 2- or V beta 10-bearing T cells. Eur J Immunol. 1991 Dec;21(12):3035–3040. doi: 10.1002/eji.1830211220. [DOI] [PubMed] [Google Scholar]
- O'Neill A. E., Reid K., Garberi J. C., Karl M., Flaherty L. Extensive deletions in the Q region of the mouse major histocompatibility complex. Immunogenetics. 1986;24(6):368–373. doi: 10.1007/BF00377954. [DOI] [PubMed] [Google Scholar]
- Ohteki T., MacDonald H. R. Major histocompatibility complex class I related molecules control the development of CD4+8- and CD4-8- subsets of natural killer 1.1+ T cell receptor-alpha/beta+ cells in the liver of mice. J Exp Med. 1994 Aug 1;180(2):699–704. doi: 10.1084/jem.180.2.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porcelli S., Brenner M. B., Greenstein J. L., Balk S. P., Terhorst C., Bleicher P. A. Recognition of cluster of differentiation 1 antigens by human CD4-CD8-cytolytic T lymphocytes. Nature. 1989 Oct 5;341(6241):447–450. doi: 10.1038/341447a0. [DOI] [PubMed] [Google Scholar]
- Porcelli S., Morita C. T., Brenner M. B. CD1b restricts the response of human CD4-8- T lymphocytes to a microbial antigen. Nature. 1992 Dec 10;360(6404):593–597. doi: 10.1038/360593a0. [DOI] [PubMed] [Google Scholar]
- Sanchez-Madrid F., Simon P., Thompson S., Springer T. A. Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1. J Exp Med. 1983 Aug 1;158(2):586–602. doi: 10.1084/jem.158.2.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scollay R. G., Butcher E. C., Weissman I. L. Thymus cell migration. Quantitative aspects of cellular traffic from the thymus to the periphery in mice. Eur J Immunol. 1980 Mar;10(3):210–218. doi: 10.1002/eji.1830100310. [DOI] [PubMed] [Google Scholar]
- Tomonari K., Lovering E., Fairchild S., Spencer S. Two monoclonal antibodies specific for the T cell receptor V alpha 8. Eur J Immunol. 1989 Jun;19(6):1131–1135. doi: 10.1002/eji.1830190625. [DOI] [PubMed] [Google Scholar]
- Tomonari K., Lovering E., Spencer S. Correlation between the V beta 4+ CD8+ T-cell population and the H-2d haplotype. Immunogenetics. 1990;31(5-6):333–339. doi: 10.1007/BF02115007. [DOI] [PubMed] [Google Scholar]
- Tough D. F., Sprent J. Turnover of naive- and memory-phenotype T cells. J Exp Med. 1994 Apr 1;179(4):1127–1135. doi: 10.1084/jem.179.4.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Unkeless J. C. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. J Exp Med. 1979 Sep 19;150(3):580–596. doi: 10.1084/jem.150.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Utsunomiya Y., Kosaka H., Kanagawa O. Differential reactivity of V beta 9 T cells to minor lymphocyte stimulating antigen in vitro and in vivo. Eur J Immunol. 1991 Apr;21(4):1007–1011. doi: 10.1002/eji.1830210422. [DOI] [PubMed] [Google Scholar]
- Van Kaer L., Ashton-Rickardt P. G., Ploegh H. L., Tonegawa S. TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell. 1992 Dec 24;71(7):1205–1214. doi: 10.1016/s0092-8674(05)80068-6. [DOI] [PubMed] [Google Scholar]
- Viville S., Neefjes J., Lotteau V., Dierich A., Lemeur M., Ploegh H., Benoist C., Mathis D. Mice lacking the MHC class II-associated invariant chain. Cell. 1993 Feb 26;72(4):635–648. doi: 10.1016/0092-8674(93)90081-z. [DOI] [PubMed] [Google Scholar]
- White J., Blackman M., Bill J., Kappler J., Marrack P., Gold D. P., Born W. Two better cell lines for making hybridomas expressing specific T cell receptors. J Immunol. 1989 Sep 15;143(6):1822–1825. [PubMed] [Google Scholar]
- Yoshimoto T., Paul W. E. CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3. J Exp Med. 1994 Apr 1;179(4):1285–1295. doi: 10.1084/jem.179.4.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zubler R. H., Lowenthal J. W., Erard F., Hashimoto N., Devos R., MacDonald H. R. Activated B cells express receptors for, and proliferate in response to, pure interleukin 2. J Exp Med. 1984 Oct 1;160(4):1170–1183. doi: 10.1084/jem.160.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de la Salle H., Hanau D., Fricker D., Urlacher A., Kelly A., Salamero J., Powis S. H., Donato L., Bausinger H., Laforet M. Homozygous human TAP peptide transporter mutation in HLA class I deficiency. Science. 1994 Jul 8;265(5169):237–241. doi: 10.1126/science.7517574. [DOI] [PubMed] [Google Scholar]