Expression and function of transgenic HLA-DQ molecules and lymphocyte development in mice lacking invariant chain

Govindarajan Rajagopalan, Michele K. Smart, Christopher J. Krco, Chella S. David

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Invariant chain (Ii) is a non-MHC-encoded molecule, which plays an accessory role in the proper assembly/expression of functional MHC class II molecules and there by plays an important role in Ag processing/presentation. The phenotype of mice lacking Ii depends on the allotype of the MHC class II molecule. In some mice strains, Ii deficiency results in reduction in expression of class II molecules accompanied by defective CD4+ T cell development. Responses to conventional Ags/superantigens are also compromised. In this study, we describe for the first time the functionality of human class II molecules, HLA-DQ6 and HLA-DQ8, in transgenic mice lacking Ii. HLA transgenic Ii-/- mice expressed very low levels of surface DQ6 and DQ8 accompanied by severe reduction in CD4+ T cells both in the thymus and periphery. In vitro proliferation and cytokine production to an exogenous superantigen, staphylococcal enterotoxin B (SEB) was diminished in HLA-transgenic Ii-/- mice. However, SEB-induced in vivo expansion of CD8+ T cells expressing TCR Vβ8 family in DQ8.Ii-/- mice was comparable with that of DQ8.Ii+/+ mice. Systemic IFN-γ production following in vivo challenge with SEB was reduced in DQ8.Ii-/- mice and were also protected from SEB-induced toxic shock. Although the T cell response to a known peptide Ag was diminished in DQ8.Ii-/- mice, DQ8.Ii-/- APCs were capable of presenting that peptide to primed T cells from wild-type DQ8 mice as well as to a specific T cell hybridoma. Differentiation of mature B cells was also affected to a certain extent in DQ8.Ii-/- mice.

Original languageEnglish (US)
Pages (from-to)1774-1783
Number of pages10
JournalJournal of Immunology
Volume169
Issue number4
StatePublished - Aug 15 2002

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HLA-DQ Antigens
Lymphocytes
T-Lymphocytes
Transgenic Mice
Superantigens
Peptides
invariant chain
Hybridomas
Septic Shock
Thymus Gland
B-Lymphocytes
Cytokines
Phenotype
staphylococcal enterotoxin B

ASJC Scopus subject areas

  • Immunology

Cite this

Rajagopalan, G., Smart, M. K., Krco, C. J., & David, C. S. (2002). Expression and function of transgenic HLA-DQ molecules and lymphocyte development in mice lacking invariant chain. Journal of Immunology, 169(4), 1774-1783.

Expression and function of transgenic HLA-DQ molecules and lymphocyte development in mice lacking invariant chain. / Rajagopalan, Govindarajan; Smart, Michele K.; Krco, Christopher J.; David, Chella S.

In: Journal of Immunology, Vol. 169, No. 4, 15.08.2002, p. 1774-1783.

Research output: Contribution to journalArticle

Rajagopalan, G, Smart, MK, Krco, CJ & David, CS 2002, 'Expression and function of transgenic HLA-DQ molecules and lymphocyte development in mice lacking invariant chain', Journal of Immunology, vol. 169, no. 4, pp. 1774-1783.
Rajagopalan, Govindarajan ; Smart, Michele K. ; Krco, Christopher J. ; David, Chella S. / Expression and function of transgenic HLA-DQ molecules and lymphocyte development in mice lacking invariant chain. In: Journal of Immunology. 2002 ; Vol. 169, No. 4. pp. 1774-1783.
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