Vet Pathol 38:611-619 (2001)
© 2001 American College of Veterinary Pathologists
Review Article
CD1—The Pathology Perspective
S.M. Rhind
Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Midlothian, UK
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Abstract
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CD1 molecules are a family of cell surface-associated glycoproteins now recognized as having a role in antigen presentation. These glycoproteins are distinct from yet have some similarities to classical major histocompatibility complex class I and class II molecules. The role of these molecules has been studied in detail over recent years, with an explosion of interest following the demonstration that they can present nonprotein antigens to certain subpopulations of T cells. The purpose of this paper is to provide an overview of current knowledge of the function of the CD1 family with specific emphasis on the potential role in the pathogenesis of certain diseases. Although much of the current research in this field has inevitably concentrated on mice and humans, this work also has potential significance for veterinary species.
Key words: CD1; conserved antigens; disease; mycobacteria; pathology.
The CD1 family comprises five distinct genes, A–E, which are variably conserved across the species. The family can be broadly divided into two groups—the CD1A-C group (group 1) and the CD1D group (group 2). Sequencing of CD1E (only identified in humans and guinea pigs to date) indicates that this is an intermediate group with similarities to both group 1 and group 2.13,16 Mice and rats only possess members of the CD1D group, and humans, sheep, and rabbits possess members of both groups. Recent molecular studies in the pig have identified a gene (pCD1.1) that is relatively dissimilar to other CD1 isotypes and moreover contains a major histocompatibility complex (MHC) class I-like cytoplasmic tail.15 A summary of current knowledge of CD1 genes and proteins across species is presented in Table 1. With the apparent exception of the guinea pig,16 there is evolutionary conservation of CD1d antigens, consistent with a key role for these molecules in the immune response.11 More recent studies have begun to extend the initial immunologic characterization of these molecules and to address the significance of this axis of the immune system in the pathogenesis of a range of diseases.
The details of the immunology of these molecules have been extensively reviewed recently.9,36,37 Here, I provide only a brief overview as a prerequisite to the understanding of the pathologic significance of CD1. I then review the role of CD1 in disease pathogenesis with more detailed discussion of the implications and potential significance for the future in terms of veterinary pathology.
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CD1 Structure and Function
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A highly relevant feature of these molecules in their remarkable lack of polymorphism, totally unlike classical MHC class I and class II molecules, which are inherently polymorphic. In the early days of CD1 research, this lack of variability in MHC-related molecules was perceived to reflect possible functional redundancy of the population27; however, it is now clear that this feature provides vital clues to the role of these molecules. CD1 molecules are structurally similar to MHC molecules, in particular to MHC class I molecules, with which they share a closely similar exon arrangement and corresponding morphology (Fig. 1). The recent resolution of the crystal structure of mouse CD1 demonstrated that the structure is more closely related to that of MHC class I than to that of MHC class II. The binding groove, although significantly narrower, is substantially larger because of increased depth and it has only two major pockets that are almost completely hydrophobic.56 This structure provides a classical antigen-presenting architecture allowing fragments of antigenic material to be presented on the cell surface, where appropriate T cells can be triggered on recognition of the antigen.
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Fig. 1. Exon arrangement of CD1 and translation to protein structure showing antigen-binding groove (ABG) created by the alpha 1 and alpha 2 domains. Note also the noncovalent association with ß2-microglobulin. TM = transmembrane; Cyt = cytoplasmic; UT = untranslated.
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T-cell Recognition of CD1
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There has been much work carried out on the nature of the T cells capable of recognizing CD1, a detailed discussion of which is outside the scope of this review; however, the gamma delta (
), double negative (DN), and natural killer (NK) T cells have all been linked with recognition of CD1 molecules. The key feature common to many of these cells is expression of a relatively invariant T-cell receptor (consistent with recognition of conserved antigen and an invariant presentation molecule). The DN subset is characterized by lack of expression of both CD4 and CD8 molecules. These cells can express either 
ß or receptors and many are relatively invariant.
The T-cell population has attracted much interest with regard to potential recognition of CD1 molecules. These cells have marked interspecies differences in numbers and location and are present in notably large numbers in young ruminants.21 In humans, a major subset of T cells recognize CD1c molecules,48 although significant functional studies on the relationship between CD1 molecules and T cells have yet to be carried out in animals. NK T cells are a specialized population of T cells that coexpress receptors of the NK lineage. These cells are distinct from natural killer cells, with which they share some common receptors.8 The NK T cells have a remarkable capacity to rapidly secrete large amounts of cytokines (notably Interleukin 4 [IL-4] and Interferon [IFN]) and can thus rapidly regulate Th1/Th2 differentiation.7 Many of these cells are reactive to CD1 molecules.6 A further intriguing feature of these cells is autoreactivity; exogenous antigen is not always required to elicit a CD1-restricted response.
The functional relevance of this CD1 recognition by specific T-cell subsets provides the immune system with a mechanism for rapid response to nonpolymorphic molecules, consistent with a key role in innate immunity prior to the onset of the definitive acquired immune response.
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CD1 Expression
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In broad terms, CD1 expression can be divided into two categories on the basis of anatomic localization: strong expression on cortical thymocyte populations and expression on a variety of antigen-presenting cells (APCs), notably dendritic cells, B cells, and monocytes. There is interisotype and interspecies variation in CD1 expression, and monoclonal antibodies (mAbs) can be used to readily demonstrate this feature across many species. With the exception of the mouse (which for reasons of limited expression is not a good model for the system), the animal species with one of the best characterized CD1 families is the sheep, in which studies of expression at the cellular and molecular level have been carried out.18,39,40 CD1 molecules have been identified using mAbs in other species, including the cat,53 dog,34,35 pig,17,42 and horse.45 Most CD1 molecules are expressed at high levels in the thymus. Using the mAb IAH-CC20 (which recognizes CD1b23), strong expression of CD1 is evident in cortical thymocytes of ruminants, dogs, and horses (Fig. 2).
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Fig. 2. Thymus; horse. Strong staining of cortical thymocytes for group 1 CD1 (mAb CC20). Avidin–biotin–peroxidase complex method, Mayer's hematoxylin counterstain. Bar = 50 µm.
Fig. 3. Lymph node; dog. Staining of paracortical dendritic cells for group 1 CD1 (mAb CC20). Avidin–biotin–peroxidase complex method, Mayer's hematoxylin counterstain. Bar = 100 µm.
Fig. 4. Lung; sheep. In situ hybridization using conserved (alpha 3 domain) antisense digoxigenin-labeled riboprobe showing positive bronchiole–associated lymphoid tissue lymphocytes. Developed using antidigoxigenin alkaline phosphatase; nitroblue tetrazolium/bromochloroindelyl phosphate method. Bar = 50 µm.
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Figure 3 demonstrates CD1 staining on canine dendritic cells using the mAb IAH-CC20. In addition to the use of mAbs to study surface expression of these molecules, our work in sheep has utilized in situ hybridization to identify expression in a wide range of cells including B cells (e.g., in bronchus/bronchiole-associated lymphoid tissue, Fig. 4) and in central nervous system (CNS) microglial cells and neuronal cell bodies.41
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CD1 and Antigen Presentation
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Although the precise mechanism for antigen presentation has not currently been elucidated, it is now generally accepted that CD1 molecules have evolved to provide an extra arm to the immune response by virtue of their ability to present lipid/glycolipid-derived and hydrophobic antigens. The recent resolution of the crystal structure of mouse CD1d demonstrated a deep antigen-binding groove, implying that presentation occurs in a fashion broadly similar to that of classical MHC molecules.56 In simplistic terms, the presentation of lipid by CD1 molecules can be broadly divided into two categories: that derived from infectious agents (principally bacterial and parasitic) and self lipid. Research to date suggests that bacteria-derived antigens are presented by group 1 CD1 molecules rather than group 2 molecules.43 Figure 5 illustrates examples of proposed mechanisms and downstream consequences of this presentation, whereby presentation of bacterial antigens elicits IFN production and a Th1-type response, with ultimate killing of infected macrophages14,29,50 (Fig. 5A). In contrast, presentation of self lipid may be more likely to elicit a Th2-type response, with resultant rapid production of cytokines by responding populations of NK T cells (Fig. 5B).
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Fig. 5. Schematic of different potential roles of group 1 versus group 2 CD1 molecules. Current evidence suggests that group 1 CD1 recognition is directly involved in removal of infected APCs (A) in contrast to group 2 recognition which has an indirect regulatory role (B).
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Presentation of foreign lipid
Mycobacteria.
In terms of specific infectious agents, most research has focused on mycobacterial disease, with detailed biochemical analysis of the microbial lipids involved.12,20,32,33 The identification of the capacity for CD1 molecules to bind hydrophobic ligands, notably bacteria-derived lipid/glycolipid, has been extended to show definitively that CD1 molecules effectively sample mycobacterial glycolipids from intracellular sites within infected cells.43 Infection of APCs with Mycobacterium tuberculosis downregulates the expression of human CD1b, suggesting the presence of a novel evasion mechanism of M. tuberculosis that could contribute to persistence of intracellular infection by avoiding immune recognition.51
Research has only relatively recently turned from this basic immunologic characterization toward assessment of the role and significance of this CD1-mediated presentation in vivo in naturally occurring disease situations. In humans, study of the role of CD1 in the pathogenesis of leprosy has revealed that expression of CD1 is correlated with effective immunity to Mycobacterium leprae.46,47 Investigation of CD1 expression in sheep with ovine paratuberculosis has shown a similar upregulation of CD1 expression in association with the tuberculoid form of the disease.38 In addition, a recent study investigated both the expression of CD1 molecules (group 1) and T cells in a model of ovine paratuberculosis.4 Levels of T cells increased to a significant level, and a decrease was observed in the number of CD1 cells in the jejunal Peyer's patch of the infected group. Although this decrease was not significant, it may represent a mild in vivo illustration of a downregulation mechanism employed by M. tuberculosis.
Overall, these findings are consistent with a role for CD1 in ensuring the generation of an effective cell-mediated immune response against mycobacteria. In addition to these studies of mycobacterial disease of humans and ruminants, mice treated with anti-CD1 mAbs show exacerbated tuberculosis lesions compared with controls.52
Other pathogens.
Although the majority of research has inevitably focused on the potential for CD1 molecules to present mycobacterial antigens, it seems unlikely that this family of molecules has been retained throughout evolution solely to provide a protective mechanism against this one class of bacteria. Obvious other candidate organisms would include organisms with similar structural elements, such as Rhodococcus and Nocardia. The palmitate hypothesis has been proposed20 whereby palmitate anchors covalently attach capsular polysaccharides from a variety of organisms into the groove of CD1. In support of this hypothesis, preliminary studies have identified CD1-restricted T-cell populations that proliferate in response to Haemophilus influenzae type b antigen.19 Other recent studies have shown that CD1d deficiency impairs host resistance to the spirochaete Borrelia burgdorferi (an organism containing proinflammatory lipid antigen).28 Glycosylphosphatidylinositol (GPI) has been eluted from murine CD1d,25 and this compound is present in several protozoan parasites, including Leishmania. CD1–NK T-cell interactions are involved in regulating immunogobulin G responses to the GPI-anchored surface antigens of Plasmodium and Trypanosoma.44 These studies suggest that the specific pathogens identified thus far as having an association with CD1-presenting molecules are likely to represent the tip of the iceberg.
Presentation of self-derived lipid
In addition to the role in certain infectious diseases, CD1 molecules have also been implicated in other diseases by virtue of their capacity to present nonmicrobial lipid. The best example of this presentation is the CD1 expression associated with human atherosclerotic plaques.30 CD1 expression in these areas may indicate a role in the genesis of the lesions and may provide a mechanism for sustained T-cell activation.
A further area in which CD1 presentation of lipid has been investigated is in tumors associated with glycolipid antigens. More specifically, the relationship between the number of infiltrating CD1a-positive cells and prognosis has been investigated in tumors, including breast carcinomas, with some descriptions of an association of these cells with an improved prognosis. In particular, there is evidence that CD1a-positive cells may have a role in antigen capture and presentation within these tumors.5,22
Considering this association with lipid and lipid-related antigens, it is perhaps not surprising that studies of CD1 expression in certain CNS diseases have also identified upregulation of CD1 in this lipid-rich environment. Specifically, studies on patients with acute inflammatory demyelinating polyradiculoneuropathy showed upregulation of CD1a and CD1b on endoneurial macrophages and on myelinated nerve fibers.26 Chronic-active multiple sclerosis lesions also show prominent CD1b immunoreactivity on perivascular inflammatory cells and on hypertrophic astrocytes.3
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Role of CD1 in Immune-mediated Disease
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In addition to the role in presentation of lipid-derived antigens (either lipid from pathogens or internally derived lipid), a role for CD1 molecules in immune-mediated disease has also been shown. In particular the two broad areas of allergic/atopic disease and autoimmune disease have been investigated.
NK T cells reactive with group 2 CD1 molecules can produce large amounts of IL-4,6,54 thus supporting the hypothesis that these molecules are involved in allergic diseases by virtue of skewing the immune response towards the Th2 pathway (Fig. 5B). Also in support of this hypothesis, studies on alveolar macrophages isolated from asthmatic humans have shown overexpression of CD1,2 and it has been hypothesized that both T cells and CD1 expression contribute to atopic status in some individuals.49
Studies on contact hypersensitivity in sheep have shown CD1 expression both on and in close association with vascular endothelium, consistent with a role in antigen presentation during the dermatitis reaction.24 In humans, studies on lesions of psoriasis have identified overexpression of CD1d in chronic-active plaques.10 In contrast to the restricted and low level of expression in normal skin, CD1d expression was induced in these lesions and also in response to physical trauma and contact sensitizing agents.
With regard to autoimmune disease, most data are from studies on genetically modified mice,31,55 e.g., genetically engineered mice predisposed to development of lupus exhibit CD1-dependant production of autoantibody.55 Nevertheless, there is sufficient evidence to suggest that there may be a role for the CD1 axis in genuine naturally occurring autoimmune and allergic disease.
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CD1 Expression in Reactive and Neoplastic Populations
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In addition to the role of CD1 as an antigen-presenting molecule and resultant involvement in infectious and immune-mediated disease, expression of CD1 has also been used to confirm the histogenesis of certain neoplastic populations. CD1 expression by neoplastic cells has been demonstrated in canine cutaneous histiocytoma, establishing the origin of this tumor as a Langerhans cell histiocytosis.35 Although this example illustrates the use of CD1 mAbs for simplistic cell phenotyping, more recent studies have defined canine cutaneous and systemic histiocytosis as two clinical manifestations of a reactive population of CD1-positive dermal dendritic cells, and immune dysregulatory mechanisms are thought to be involved in the genesis of the lesion.1 It is tempting to speculate that CD1 as a recognized antigen-presenting molecule expressed on potent APCs (dendritic cells) may be involved in lesion development.
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Conclusion
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CD1 molecules are an intriguing family of antigen-presenting molecules whose importance in the pathogenesis of certain diseases is only beginning to be elucidated. Although there is much focus currently on their role in presentation of mycobacteria-derived lipids, it is unlikely that the evolutionary conservation that is a feature of this family relates to a role solely as presenters of molecules from such a specific group of pathogens. It is more likely that the diseases in which CD1 molecules have been shown to be important represent the tip of the iceberg. Further research is needed into the relevance of this arm of the immune response to immune-mediated (in particular autoimmune) disease and how these molecules might guide the immune response along advantageous or detrimental pathways. This research would be aided by investigation of CD1 expression patterns in various diseases in domestic rather than laboratory species, in particular in view of the recognized dissimilarities between the rodent CD1 system and those of other veterinary species. Many questions pertaining to the CD1 system remain to be answered. In particular it would be desirable to establish the CD1 status of domestic animals with the aim of facilitating subsequent investigations into the role of these molecules in infectious and immune-mediated disease.
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Acknowledgments
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I am grateful to J. Hopkins for critical review of the manuscript.
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References
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- Affolter VK, Moore PF: Canine cutaneous and systemic histiocytosis—reactive histiocytosis of dermal dendritic cells. Am J Dermatopathol 22:40-48, 2000[CrossRef][Medline]
- Agea E, Forenza N, Piattoni S, Russano A, Monaco A, Flenghi L, Bistoni O, Gillies DA, Azuma M, Bertotta A, Spinozzi F: Expression of B7 co-stimulatory molecules and CD1a antigen by alveolar macrophages in allergic bronchial asthma. Clin Exp Allergy 28:1359-1367, 1998[CrossRef][Medline]
- Battistini L, Fischer FR, Raine CS, Brosnan CF: CD1b is expressed in multiple sclerosis lesions. J Neuroimmunol 67:145-151, 1996[Medline]
- Beard P, Rhind S, Sinclair MC, Wildblood LA, Stevenson K, McKendrick IJ, Sharp JM, Jones DG: Modulation of T cells and CD1 in Mycobacterium avium subsp p paratuberculosis infection. Vet Immunol Immunopathol 77:311-319, 2000[CrossRef][Medline]
- Becker Y: Anticancer role of dendritic cells (Dc) in human and experimental cancers—a review. Anticancer Res 12:511-520, 1992[Medline]
- Bendelac A, Lantz O, Quimby ME, Yewdell JW, Bennink JR, Brutkiewicz RR: CD1 recognition by mouse NK1(+) T-lymphocytes. Science 268:863-865, 1995[Abstract/Free Full Text]
- Bendelac A, Rivera MN, Park SH, Roark JH: Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 15:535-562, 1997[CrossRef][Medline]
- Bix M, Locksley RM: Natural T-cells—cells that coexpress NKRP-1 and TCR. J Immunol 155:1020-1022, 1995[Medline]
- Blumberg RS, Gerdes D, Chott A, Porcelli SA, Balk SP: Structure and function of the CD1 family of MHC-like cell-surface proteins. Immunol Rev 147:5-29, 1995[CrossRef][Medline]
- Bonish B, Jullien D, Dutronc Y, Huang BB, Modlin R, Spada FM, Porcelli SA, Nickoloff BJ: Overexpression of CD1d by keratinocytes in psoriasis and CD1d-dependent IFN-gamma production by NK-T cells. J Immunol 165:4076-4082, 2000[Abstract/Free Full Text]
- Brossay L, Kronenberg M: Highly conserved antigen-presenting function of CD1d molecules. Immunogenetics 50:146-151, 1999[CrossRef][Medline]
- Burdin N, Kronenberg M: CD1-mediated immune responses to glycolipids. Curr Opin Immunol 11:326-331, 1999[CrossRef][Medline]
- Calabi F, Jarvis JM, Martin L, Milstein C: 2 Classes of CD1 genes. Eur J Immunol 19:285-292, 1989[Medline]
- Cho S, Mehra V, Thoma-Uszynski S, Stenger S, Serbina N, Mazzaccaro RJ, Flynn JL, Barnes PF, Southwood S, Celis E, Bloom BR, Modlin RL, Sette A: Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis. Proc Natl Acad Sci USA 97:12210-12215, 2000[Abstract/Free Full Text]
- Chun T, Wang K, Zuckermann FA, Gaskins HR: Molecular cloning and characterization of a novel CD1 gene from the pig. J Immunol 162:6562-6571, 1999[Abstract/Free Full Text]
- Dascher CC, Hiromatsu K, Naylor JW, Brauer PP, Brown KA, Storey JR, Behar SM, Kawasaki ES, Porcelli SA, Brenner MB, LeClair KP: Conservation of a CD1 multigene family in the guinea pig. J Immunol 163:5478-5488, 1999[Abstract/Free Full Text]
- Denham S, Shimizu M, Bianchi ATJ, Zwart RJ, Carr MM, Parkhouse RME: Monoclonal antibodies recognizing differentiation antigens on porcine B-cells. Vet Immunol Immunopathol 43:259-267, 1994[CrossRef][Medline]
- Dutia BM, Hopkins J: Analysis of the CD1 cluster in sheep. Vet Immunol Immunopathol 27:189-194, 1991[CrossRef][Medline]
- Fairhurst RM, Wang CX, Sieling PA, Modlin RL, Braun J: CD1 presents antigens from a gram-negative bacterium, Haemophilus influenzae type b. Infect Immun 66:3523-3526, 1998[Abstract/Free Full Text]
- Fairhurst RM, Wang CX, Sieling PA, Modlin RL, Braun J: CD1-restricted T cells and resistance to polysaccharide-encapsulated bacteria. Immunol Today 19:257-259, 1998[CrossRef][Medline]
- Hein WR, Mackay CR: Prominence of gamma-delta T-cells in the ruminant immune system. Immunol Today 12:30-34, 1991[CrossRef][Medline]
- Hillenbrand EE, Neville AM, Coventry BJ: Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours. Br J Cancer 79:940-944, 1999[CrossRef][Medline]
- Howard CJ, Sopp P, Bembridge G, Young J, Parsons KR: Comparison of CD1 monoclonal antibodies on bovine cells and tissues. Vet Immunol Immunopathol 39:77-83, 1993[CrossRef][Medline]
- Jorundsson E, Press CM, Landsverk T: Distribution of MHC-II and CD1 molecules in the skin of lambs and changes during experimentally-induced contact hypersensitivity. Vet Immunol Immunopathol 74:87-101, 2000[CrossRef][Medline]
- Joyce S, Woods AS, Yewdell JW, Bennink JR, De Silva AD, Boesteanu A, Balk SP, Cotter RJ, Brutkiewicz RR: Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. Science 279:1541-1544, 1998[Abstract/Free Full Text]
- KhaliliShirazi A, Gregson NA, Londei M, Summers L, Hughes RAC: The distribution of CD1 molecules in inflammatory neuropathy. J Neurol Sci 158:154-163, 1998[CrossRef][Medline]
- Klein J, Zhu Z, Gutknecht J, Figueroa F, Kasahra M: MHC: lessons in evolution. In: Immunogenetics of the Major Histocompatibility Complex, ed. Srivastava R, pp 18-38, VCH, Cambridge, UK 1991
- Kumar H, Belperron A, Barthold SW, Bockenstedt LK: Cutting edge: CD1d deficiency impairs murine host defense against the spirochete Borrelia burgdorferi. J Immunol 165:4797-4801, 2000[Abstract/Free Full Text]
- Mazzaccaro RJ, Stenger S, Rock KL, Porcelli SA, Brenner MB, Modlin RL, Bloom BR: Cytotoxic T lymphocytes in resistance to tuberculosis. In: Mechanisms of Lymphocyte Activation and Immune Regulation VII, vol. 452, pp 85-101, 1998
- Melian A, Geng YJ, Sukhova GK, Libby P, Porcelli SA: CD1 expression in human atherosclerosis—a potential mechanism for T cell activation by foam cells. Am J Pathol 155:775-786, 1999[Abstract/Free Full Text]
- Mieza MA, Itoh T, Cui JQ, Makino Y, Kawano T, Tsuchida K, Koike T, Shirai T, Yagita H, Matsuzawa A, Koseki H, Taniguchi M: Selective reduction of V alpha 14(+) NK T cells associated with disease development in autoimmune-prone mice. J Immunol 156:4035-4040, 1996[Abstract]
- Moody DB, Guy MR, Grant E, Cheng TY, Brenner MB, Besra GS, Porcelli SA: CD1b-mediated T cell recognition of a glycolipid antigen generated from mycobacterial lipid and host carbohydrate during infection. J Exp Med 192:965-976, 2000[Abstract/Free Full Text]
- Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA: CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature 404:884-888, 2000[CrossRef][Medline]
- Moore PF, Olivry T, Naydan D: Canine cutaneous epitheliotropic lymphoma (mycosis fungoides) is a proliferative disorder of CD8(+) T-cells. Am J Pathol 144:421-429, 1994[Abstract]
- Moore PF, Schrenzel MD, Affolter VK, Olivry T, Naydan D: Canine cutaneous histiocytoma is an epidermotropic Langerhans cell histiocytosis that expresses CD1 and specific beta(2)-integrin molecules. Am J Pathol 148:1699-1708, 1996[Abstract]
- Porcelli SA: The CD1 family—a 3rd lineage of antigen-presenting molecules. Adv Immunol 59:1-98, 1995[Medline]
- Porcelli SA, Segelke BW, Sugita M, Wilson IA, Brenner MB: The CD1 family of lipid antigen-presenting molecules. Immunol Today 19:362-368, 1998[CrossRef][Medline]
- Rhind SM: Molecular Analysis of Ovine CD1 Expression. University of Edinburgh, Edinburgh, UK 1996
- Rhind SM, Dutia BM, Howard CJ, Hopkins J: Discrimination of 2 subsets of CD1 molecules in the sheep. Vet Immunol Immunopathol 52:265-270, 1996[CrossRef][Medline]
- Rhind SM, Hopkins J, Dutia BM: Amino-terminal sequencing of sheep CD1 antigens and identification of a sheep CD1D gene. Immunogenetics 49:225-230, 1999[CrossRef][Medline]
- Rhind SM, Hopkins J, Grant ES: Differential expression of ovine CD1. Immunology 101:452-457, 2000[CrossRef][Medline]
- Salmon H, Johnson I, Germana S, Haller GW, Sachs DH, Leguern C: Dendritic cells enriched from swine thymus co-express CD1, CD2 and major histocompatibility complex class II and actively stimulate alloreactive T lymphocytes. Scand J Immunol 52:164-172, 2000[CrossRef][Medline]
- Schaible UE, Kaufmann SHE: CD1 and CD1-restricted T cells in infections with intracellular bacteria. Trends Microbiol 8:419-425, 2000[CrossRef][Medline]
- Schofield L, McConville MJ, Hansen D, Campbell AS, Fraser-Reid B, Grusby MJ, Tachado SD: CD1d-restricted immunoglobulin G formation to GPI-anchored antigens mediated by NKT cells. Science 283:225-229, 1999[Abstract/Free Full Text]
- Siedek E, Little S, Mayall S, Edington N, Hamblin A: Isolation and characterisation of equine dendritic cells. Vet Immunol Immunopathol 60:15-31, 1997[CrossRef][Medline]
- Sieling PA, Jullien D, Dahlem M, Tedder TF, Rea TH, Modlin RL, Porcelli SA: CD1 expression by dendritic cells in human leprosy lesions: correlation with effective host immunity. J Immunol 162:1851-1858, 1999[Abstract/Free Full Text]
- Sieling PA, Ochoa MT, Jullien D, Leslie DS, Sabet S, Rosat JP, Burdick AE, Rea TH, Brenner MB, Porcelli SA, Modlin RL: Evidence for human CD4(+) T cells in the CD1-restricted repertoire: derivation of mycobacteria-reactive T cells from leprosy lesions. J Immunol 164:4790-4796, 2000[Abstract/Free Full Text]
- Spada FM, Grant EP, Peters PJ, Sugita M, Melian A, Leslie DS, Lee HK, van Donselaar E, Hanson DA, Krensky AM, Majdic O, Porcelli SA, Morita CT, Brenner MB: Self-recognition of CD1 by gamma/delta T cells: implications for innate immunity. J Exp Med 191:937-948, 2000[Abstract/Free Full Text]
- Spinozzi F, Agea E, Bistoni O, Forenza N, Bertotto A: Gamma delta T cells, allergen recognition and airway inflammation. Immunol Today 19:22-26, 1998[CrossRef][Medline]
- Stenger S, Mazzaccaro RJ, Uyemura K, Cho S, Barnes PF, Rosat JP, Sette A, Brenner MB, Porcelli SA, Bloom BR, Modlin RL: Differential effects of cytolytic T cell subsets on intracellular infection. Science 276:1684-1687, 1997[Abstract/Free Full Text]
- Stenger S, Niazi KR, Modlin RL: Down-regulation of CD1 on antigen-presenting cells by infection with Mycobacterium tuberculosis. J Immunol 161:3582-3588, 1998[Abstract/Free Full Text]
- Szalay G, Zugel U, Ladel CH, Kaufmann SHE: Participation of group 2 CD1 molecules in the control of murine tuberculosis. Microbes Infect 1:1153-1157, 1999[CrossRef][Medline]
- Woo JC, Moore PF: A feline homologue of CD1 is defined using a feline-specific monoclonal antibody. Tissue Antigens 49:244-251, 1997[Medline]
- Yoshimoto T, Paul WE: CD4(pos), NK1.1(pos) T-cells promptly produce interleukin-4 in response to in-vivo challenge with anti-CD3. J Exp Med 179:1285-1295, 1994[Abstract/Free Full Text]
- Zeng D, Lee MK, Tung J, Brendolan A, Strober S: Cutting edge: a role for CD1 in the pathogenesis of lupus in NZB/NZW mice. J Immunol 164:5000-5004, 2000[Abstract/Free Full Text]
- Zeng ZH, Castano AR, Segelke BW, Stura EA, Peterson PA, Wilson IA: Crystal structure of mouse CD1: an MHC-like fold with a large hydrophobic binding groove. Science 277:339-345, 1997[Abstract/Free Full Text]
Request reprints from Dr. S. Rhind, Department of Veterinary Pathology, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Veterinary Centre, Midlothian EH25 9RG (Scotland).
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Abstract
CD1 Structure and Function
