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2. Cytotoxic T Lymphocyte Responses Against Measles Virus

Author

UytdeHaag, F. G. C. M., van Binnendijk, R. S., Kenter, M. J. H., Osterhaus, A. D. M. E., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, and Oldstone, Michael B. A., editor

Published
1994
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10. Human peptide transporter deficiency: importance of HLA-B in the presentation of TAP-independent EBV antigens

Author

Delasalle, H., Houssaint, E., Peyrat, Ma, Arnold, D., Salamero, J., Pinczon, D., Stevanovic, S., Bausinger, H., Fricker, D., Gomard, E., Biddison, W., Lehner, P., Uytdehaag, F., Sasportes, M., Donato, L., Rammensee, Hg, Jean-Pierre Cazenave, Hanau, D., Tongio, Mm, Bonneville, M., and Virology

Subjects
Immunology, Immunology and Allergy
Abstract

Two siblings with a peptide TAP deficiency were recently described. Despite poor cell surface expression of HLA class I molecules, these patients were not unusually susceptible to viral infections. The majority of the cell surface-expressed class I molecules were HLA-B products as assessed by cytofluorometry and biochemical analysis. Analysis of two peptides eluted from the class I molecules expressed by TAP-deficient EBV B lymphoblastoid cell lines indicated that both were derived from cytosolic proteins and presented by HLA-B molecules. Peripheral alphabeta CD8+ T cells were present and their TCR repertoire was polyclonal. Most of the alphabeta CD8+ T cell clones studied (21 of 22) were nonreactive against cells expressing normal levels of the same HLA alleles as those of the TAP-deficient patients. However, it was possible to isolate one cytotoxic CD8+ alphabeta T cell clone recognizing the EBV protein LMP2 presented by HLA-B molecules on TAP-deficient cells. These observations suggest that in the TAP-deficient patients, CD8+ alphabeta T cells could mature and be recruited in immune responses to mediate HLA class I-restricted cytotoxic defense against viral infections. They also strengthen the physiologic importance of a TAP-independent processing pathway of the LMP2 protein, which was previously shown to contain several other TAP-independent epitopes.

Published
1997
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15. Exploiting the Natural Diversity in Adenovirus Tropism for Therapy and Prevention of Disease

Author

Havenga, M. J. E., primary, Lemckert, A. A. C., additional, Ophorst, O. J. A. E., additional, van Meijer, M., additional, Germeraad, W. T. V., additional, Grimbergen, J., additional, van den Doel, M. A., additional, Vogels, R., additional, van Deutekom, J., additional, Janson, A. A. M., additional, de Bruijn, J. D., additional, Uytdehaag, F., additional, Quax, P. H. A., additional, Logtenberg, T., additional, Mehtali, M., additional, and Bout, A., additional

Published
2002
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16. Maintenance of immunological memory: A role for CD5+ B cells?

Author

UytdeHaag, F., Heijden, R.W.J. (Roger) van der, Osterhaus, A.D.M.E. (Albert), UytdeHaag, F., Heijden, R.W.J. (Roger) van der, and Osterhaus, A.D.M.E. (Albert)

Abstract

How memory is retained is an immunological mystery. One possibility, argued here by Fons UytdeHaag and colleagues, is that memory is imprinted in the somatically-mutated Ig expressed by certain CD5+ B cells. The theory proposes that the Ig expressed by this self-renewing population acts as surrogate antigen, selecting and stimulating emerging antigen-specific lymphocytes.

Published
1991
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17. Rabies virus cross-reactive murine T cell clones: analysis of helper and delayed-type hypersensitivity function.

Author

Bunschoten, H., Dietzschold, B., Claassen, I.J.Th.M. (Ivo), Klapmuts, R., UytdeHaag, F., Osterhaus, A.D.M.E. (Albert), Bunschoten, H., Dietzschold, B., Claassen, I.J.Th.M. (Ivo), Klapmuts, R., UytdeHaag, F., and Osterhaus, A.D.M.E. (Albert)

Abstract

Three T cell clones derived from rabies virus-immunized BALB/c mice were analysed for specificity and function. The clones proved to be broadly cross-reactive by responding to different rabies virus isolates (PM, ERA, CVS, HEP) and other representatives of the genus Lyssavirus, like the Duvenhage-6 (DUV6) and Mokola (MOK) viruses. The clones detected three different epitopes: an epitope expressed on the matrix protein (M) shared by PM, HEP, MOK and DUV6 viruses (clone AA8), an epitope expressed on the M-protein shared by PM, ERA, CVS, HEP and MOK viruses (clone 35A) and finally an epitope expressed on the glycoprotein (G-protein) shared by PM, ERA, CVS, HEP and MOK viruses (clone BG2). Antigen recognition of all clones proved to be MHC-restricted and they all displayed the CD4+ CD8- phenotype. Intravenous inoculation of the T cells in syngeneic mice, which had been injected intracutaneously in the ear with HEP virus, resulted in a localized DTH reaction characteristic for TH1 cells. In vitro, the clones were able to provide help to rabies virus-primed B cells, resulting in the production of virus-specific antibodies directed against all the four structural proteins of rabies virus. Further analysis of this antibody response revealed that part of it was directed against antigenic determinants of the G-protein which induce virus neutralizing antibody.

Published
1990

18. Human peptide transporter deficiency: importance of HLA-B in the presentation of TAP-independent EBV antigens.

Author

de la Salle, H, primary, Houssaint, E, additional, Peyrat, M A, additional, Arnold, D, additional, Salamero, J, additional, Pinczon, D, additional, Stevanovic, S, additional, Bausinger, H, additional, Fricker, D, additional, Gomard, E, additional, Biddison, W, additional, Lehner, P, additional, UytdeHaag, F, additional, Sasportes, M, additional, Donato, L, additional, Rammensee, H G, additional, Cazenave, J P, additional, Hanau, D, additional, Tongio, M M, additional, and Bonneville, M, additional

Published
1997
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34. Functional analysis of the defective T cell regulation of the antigen-specific PFC response in SLE patients: Differentiation of suppressor precursor cells to suppressor effector cells.

Author

Heijnen, Cobi J., Pot, K.H., Kater, L., Kluin-Nelemans, Hanneke C., Uytdehaag, F., and Ballieux, R.E.

Subjects
SYSTEMIC lupus erythematosus, PERSISTENT fetal circulation syndrome, T cells, LYMPHOCYTES, FETAL heart abnormalities, AUTOIMMUNE diseases
Abstract

The investigation described here is concerned with the T cell regulation of the antigen-specific antibody response which has been studied in patients suffering from systemic lupus erythematosus (SLE). Apart from the fact that T helper cell activity was found to be less efficient, it appeared that the peripheral blood leucocytes (PBL) of patients in an active stage of the disease did not contain the suppressor precursor cell, which functions as the target cell for the inductive signal of Tμ+ suppressor inducer cells. The absence of the suppressor precursor cells in SLE patients coincided with the absence of Tγ + suppressor effector cells. Characterization of the (post-thymic) precursor cells (derived from normal donors) with the aid of monoclonal antibodies of the OKT series and several other markers pointed out that this population contains OKT4+ as well as OKT8+ cells. Further experiments demonstrated that the cells are capable of rosetting with autologous erythrocytes, and do not bear Fc receptors for IgM or IgG. Considering the various findings as a whole the conclusion is warranted that the post-thymic suppressor precursor T cell can differentiate into a suppressor effector cell only after interaction with T suppressor inducer cells. [ABSTRACT FROM AUTHOR]

Published
1982

36. A subset of HLA-B27 molecules contains peptides much longer than nonamers.

Author

Urban, R G, Chicz, R M, Lane, W S, Strominger, J L, Rehm, A, Kenter, M J, UytdeHaag, F G, Ploegh, H, Uchanska-Ziegler, B, and Ziegler, A

Abstract

An unusual monoclonal antibody (MARB4) directed against HLA-B27 that reacts with only approximately 5-20% of the cell surface HLA-B27 was used for large-scale purification of these molecules. Subsequent mass spectrometry of HLA-B27-bound peptides showed that the minor MARB4-reactive population contained peptides primarily from 900 to 4000 Da in size (approximately 8-33 amino acid residues), whereas the major HLA-B27 population contained peptides in the mass range of 900-1400 Da (approximately 8-12 amino acid residues). Thus, a subset of HLA-B27 molecules binds to peptides much longer than nonamers. Typical HLA-B27-binding peptides contain arginine in position 2. Further analysis by Edman sequencing of the pooled bound peptides revealed that the major population contained substantial amounts of arginine at positions 1 and 9 (40-50%) and exclusively arginine at position 2, as expected. The minor population of peptides also contained detectable amounts of arginine at these positions, but at the level of only approximately 10%; no marked enrichment at any position was observed. These long HLA-B27-bound peptides could represent either intermediates in the formation of nonamers or adventitiously bound peptides. Lastly, in the TAP2 mutant cell line BM36.1 transfected with HLA-B*2705, MARB4-reactive HLA-B27 molecules were absent from the cell surface, indicating that the peptide transporter was required for delivery of the long peptides. Thus, during the folding of class I heavy chains, peptides of diverse lengths are available and participating.

Published
1994
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37. Functional analysis of the defective T cell regulation of the antigen-specific PFC response in SLE patients: differentiation of suppressor precursor cells to suppressor effector cells

Author

Heijnen, C J, Pot, K H, Kater, L, Kluin-Nelemans, H C, Uytdehaag, F, and Ballieux, R E

Subjects
Phenotype, Antibody Specificity, Ovalbumin, Antibody Formation, Antibodies, Monoclonal, Humans, Lupus Erythematosus, Systemic, Hemolytic Plaque Technique, T-Lymphocytes, Regulatory, Research Article
Abstract

The investigation described here is concerned with the T cell regulation of the antigen-specific antibody response which has been studied in patients suffering from systemic lupus erythematosus (SLE). Apart from the fact that T helper cell activity was found to be less efficient, it appeared that the peripheral blood leucocytes (PBL) of patients in an active stage of the disease did not contain the suppressor precursor cells, which functions as the target cell for the inductive signal of T mu+ suppressor inducer cells. The absence of the suppressor precursor cells in SLE patients coincided with the absence of T gamma+ suppressor effector cells. Characterization of the (post-thymic) precursor cells (derived from normal donors) with the aid of monoclonal antibodies of the OKT series and several other markers pointed out that this population contains OKT4+ as well as OKT8+ cells. Further experiments demonstrated that the cells are capable of rosetting with autologous erythrocytes, and do not bear Fc receptors for IgM or IgG. Considering the various findings as a whole the conclusion is warranted that the post-thymic suppressor precursor T cell can differentiate into a suppressor effector cell only after interaction with T suppressor inducer cells.

Published
1982

38. Localization of human antigen-specific helper and suppressor function in distinct T-cell subpopulations

Author

Heijnen, C.J., UytdeHaag, F., F.H.J., and Ballieux, R.E.

Subjects
Geneeskunde
Abstract

Distinct human T-cell subpopulations were isolated and cultured in the presence of B-cells and antigens. After an incubation period of 6 days cells were tested for their capacity to secrete antigen-specific antibodies in the PFC-assay. The results indicate that the T-helper activity for the antigen-induced T-dependent B-cell differentiation is located in the Tμ-subpopulation, whereas the suppressor-cell activity is confined to the Tγ-subpopulation.

Published
1979

40. Human anti-idiotypic T lymphocyte clones are activated by autologous anti- rabies virus antibodies presented in association with HLA-DQ molecules.

Author

UytdeHaag, F., Claassen, I.J.Th.M. (Ivo), Bunschoten, H., Loggen, H., Ottenhoff, T., Teeuwsen, V., Osterhaus, A.D.M.E. (Albert), UytdeHaag, F., Claassen, I.J.Th.M. (Ivo), Bunschoten, H., Loggen, H., Ottenhoff, T., Teeuwsen, V., and Osterhaus, A.D.M.E. (Albert)

Abstract

The regulatory function of antigen-specific T cells in human antibody responses to protein and carbohydrate determinants of many viral and bacterial antigens has extensively been studied in systems involving in vitro triggering of B cells by antigens or polyclonal activators. Although amply documented in experimental murine models, the existence of T helper cells with receptor specificity for idiotypic determinants of B cell immunoglobulins has not been demonstrated in a human system. We are interested in T helper cell recognition of idiotypic determinants of virus-specific antibody, secreted by human B cells in response to viral antigens, and in the role which such idiotype-specific T helper cells play, alone or in concert with virus-specific T helper cells, to regulate the antibody response. Understanding of the function of different T helper cell subsets in an anti-viral antibody response and especially of the mechanisms of idiotype recognition by T cells is important for the development, and future application in man of idiotype vaccines, the potential of which has been indicated for different pathogens in several animal species. It was realized that for the efficient characterization of each of the T helper cell subsets, the availability of cloned populations of T cells would be inevitable. Furthermore, we argued that if, as predicted by Jerne, idiotype recognizing T helper cells are involved in physiological idiotype regulation in the course of an immune response--e.g., following encounter with viru

Published
1987

46. Canine distemper virus in seals

Author

OSTERHAUS, A. D. M. E., primary, GROEN, J., additional, VRIES, P. DE, additional, UYTDEHAAG, F. G. C. M., additional, KLINGEBORN, B., additional, and ZARNKE, R., additional

Published
1988
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48. Seal vaccination success

Author

OSTERHAUS, A. D. M. E., primary, UYTDEHAAG, F. G. C. M., additional, VISSER, I. K. G., additional, VEDDER, E. J., additional, REIJNDERS, P. J. H., additional, KUIPER, J., additional, and BRUGGE, H. N., additional

Published
1989
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