The T cell response of HLA-DR transgenic mice to human myelin basic protein and other antigens in the presence and absence of human CD4

doi:10.1084/jem.181.3.867

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Altmann, D. M.
	Articles by Elliott, J. I.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Altmann, D. M.
	Articles by Elliott, J. I.


Social Bookmarking

	What's this?

ARTICLES

The T cell response of HLA-DR transgenic mice to human myelin basic protein and other antigens in the presence and absence of human CD4

DM Altmann, DC Douek, AJ Frater, CM Hetherington, H Inoko and JI Elliott
MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom.

Analysis of HLA class II transgenic mice has progressed in recent years from analysis of single chain HLA class II transgenes with expression of mixed mouse/human heterodimers to double transgenic mice expressing normal human heterodimers. Previous studies have used either HLA transgenic mice in which there is a species-matched interaction with CD4 or mice which lack this interaction. Since both systems are reported to generate HLA-restricted responses, the matter of the requirement for species-matched CD4 remains unclear. We have generated triple transgenic mice expressing three human transgenes, DRA, DRB, and CD4, and compared HLA-restricted responses to peptide between human- CD4+ (Hu-CD4+) and Hu-CD4- littermates. We saw no difference between Hu- CD4+ and Hu-CD4- groups, supporting the notion that for some responses at least the requirement for species-matched CD4 may not be absolute. Evidence for positive selection of mouse T cell receptors in HLA-DR transgenic mice came both from the acquisition of new, HLA-restricted responses to various peptides and from an increased frequency of T cells using the TCR V beta 4 gene segment. An important goal with respect to the analysis of function in HLA transgenic mice is the clarification of mechanisms which underpin the recognition of self- antigens in human autoimmune disease. As a first step towards 'humanized' disease models in HLA transgenic mice, we analyzed the responses of HLA-DR transgenic mice to the human MPB 139-154 peptide which has been implicated as an epitope recognized by T cells of multiple sclerosis patients. We obtained T cell responses to this epitope in transgenic mice but not in nontransgenic controls. This study suggests that HLA transgenic mice will be valuable in the analysis of HLA-restricted T cell epitopes implicated in human disease and possibly in the design of new disease models.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Faulkner, L., Altmann, D. M., Ellmerich, S., Huhtaniemi, I., Stamp, G., Sriskandan, S. (2007). Sexual Dimorphism in Superantigen Shock Involves Elevated TNF-{alpha} and TNF-{alpha} induced Hepatic Apoptosis. Am. J. Respir. Crit. Care Med. 176: 473-482 [Abstract] [Full Text]
von Delwig, A., Altmann, D. M, Charlton, F. G, McKie, N., Isaacs, J. D, Holmdahl, R., Robinson, J. H (2007). T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice. Ann Rheum Dis 66: 599-604 [Abstract] [Full Text]
Zou, J., Henderson, L., Thomas, V., Swan, P., Turner, A. N., Phelps, Richard. G. (2007). Presentation of the Goodpasture Autoantigen Requires Proteolytic Unlocking Steps That Destroy Prominent T Cell Epitopes. J. Am. Soc. Nephrol. 18: 771-779 [Abstract] [Full Text]
Faulkner, L., Cooper, A., Fantino, C., Altmann, D. M., Sriskandan, S. (2005). The Mechanism of Superantigen-Mediated Toxic Shock: Not a Simple Th1 Cytokine Storm. J. Immunol. 175: 6870-6877 [Abstract] [Full Text]
Ellmerich, S., Mycko, M., Takacs, K., Waldner, H., Wahid, F. N., Boyton, R. J., King, R. H. M., Smith, P. A., Amor, S., Herlihy, A. H., Hewitt, R. E., Jutton, M., Price, D. A., Hafler, D. A., Kuchroo, V. K., Altmann, D. M. (2005). High Incidence of Spontaneous Disease in an HLA-DR15 and TCR Transgenic Multiple Sclerosis Model. J. Immunol. 174: 1938-1946 [Abstract] [Full Text]
Pajot, A., Pancre, V., Fazilleau, N., Michel, M.-L., Angyalosi, G., Ojcius, D. M., Auriault, C., Lemonnier, F. A., Lone, Y.-C. (2004). Comparison of HLA-DR1-restricted T cell response induced in HLA-DR1 transgenic mice deficient for murine MHC class II and HLA-DR1 transgenic mice expressing endogenous murine MHC class II molecules. Int Immunol 16: 1275-1282 [Abstract] [Full Text]
Mycko, M. P., Waldner, H., Anderson, D. E., Bourcier, K. D., Wucherpfennig, K. W., Kuchroo, V. K., Hafler, D. A. (2004). Cross-Reactive TCR Responses to Self Antigens Presented by Different MHC Class II Molecules. J. Immunol. 173: 1689-1698 [Abstract] [Full Text]
Laub, R., Brecht, R., Dorsch, M., Valey, U., Wenk, K., Emmrich, F. (2002). Anti-Human CD4 Induces Peripheral Tolerance in a Human CD4+, Murine CD4-, HLA-DR+ Advanced Transgenic Mouse Model. J. Immunol. 169: 2947-2955 [Abstract] [Full Text]
Unnikrishnan, M., Altmann, D. M., Proft, T., Wahid, F., Cohen, J., Fraser, J. D., Sriskandan, S. (2002). The Bacterial Superantigen Streptococcal Mitogenic Exotoxin Z Is the Major Immunoactive Agent of Streptococcus pyogenes. J. Immunol. 169: 2561-2569 [Abstract] [Full Text]
Angyalosi, G., Neveu, R., Wolowczuk, I., Delanoye, A., Herno, J., Auriault, C., Pancre, V. (2001). HLA Class II Polymorphism Influences Onset and Severity of Pathology in Schistosoma mansoni-Infected Transgenic Mice. Infect. Immun. 69: 5874-5882 [Abstract] [Full Text]
Hall, F. C., Cope, A. P., Patel, S. D., Sonderstrup, G. (1999). Isolating the molecular suspect: HLA transgenic mice in the study of human autoimmune disease. Rheumatology (Oxford) 38: 697-704 [Full Text]
Wilkinson, R. J., Wilkinson, K. A., Jurcevic, S., Hills, A., Sinha, S., Sengupta, U., Lockwood, D. N.�J., Katoch, K., Altman, D., Ivanyi, J. (1999). Specificity and Function of Immunogenic Peptides from the 35-Kilodalton Protein of Mycobacterium leprae. Infect. Immun. 67: 1501-1504 [Abstract] [Full Text]
Geluk, A., Taneja, V., van Meijgaarden, K. E., Zanelli, E., Abou-Zeid, C., Thole, J. E.�R., de Vries, R. R.�P., David, C. S., Ottenhoff, T. H.�M. (1998). Identification of HLA class II-restricted determinants of Mycobacterium tuberculosis-derived proteins by using HLA-transgenic, class II-deficient mice. Proc. Natl. Acad. Sci. USA 95: 10797-10802 [Abstract] [Full Text]
Rosloniec, E. F., Brand, D. D., Myers, L. K., Whittington, K. B., Gumanovskaya, M., Zaller, D. M., Woods, A., Altmann, D. M., Stuart, J. M., Kang, A. H. (1997). An HLA-DR1 Transgene Confers Susceptibility to Collagen-induced Arthritis Elicited with Human Type II Collagen. J. Exp. Med. 185: 1113-1122 [Abstract] [Full Text]