Properties of HLA class II molecules divergently associated with Goodpasture's disease

Studies in vitro have suggested that a species barrier exists in functional interaction between human histocompatibility leukocyte antigen (HLA) class II and mouse CD4 molecules. However, whether mouse CD4+ T cells restricted by HLA class II molecules are generated in HLA class II transgenic mice and respond to peptide antigens across this barrier has remained unclear. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to influenza hemagglutinin-derived peptide 307-319 (HA 307) and Streptococcus pyogenes M12 protein-derived peptide 347-397 (M6C2), respectively. Inhibition studies with several monoclonal antibodies showed that transgenic HLA class II molecules presented these peptides to mouse CD4+ T cells. Furthermore, T cell lines specific for HA 307 or M6C2 obtained from the transgenic mice could respond to the peptide in the context of relevant HLA class II molecules expressed on mouse L cell transfectants that lack the expression of mouse MHC class II. These findings indicate that interaction between HLA class II and mouse CD4 molecules is sufficient for provoking peptide-specific HLA class II-restricted T cell responses in HLA class II transgenic mice.

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Epitopes Are the Functional Units of HLA Class II Molecules and Form the Molecular Basis for Disease Susceptibility

HLA Class II Antigens ◽

10.1007/978-3-642-70367-6_3 ◽

1986 ◽

pp. 32-48 ◽

Cited By ~ 6

Author(s):

J. Silver ◽

S. M. Goyert

Keyword(s):

Molecular Basis ◽

Disease Susceptibility ◽

Class Ii ◽

Hla Class Ii ◽

Functional Units ◽

Hla Class Ii Molecules

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B-cell-specific accumulation of inclusion bodies loaded with HLA class II molecules in patients with mucolipidosis II (I-cell disease)

Pediatric Research ◽

10.1038/s41390-018-0234-2 ◽

2018 ◽

Vol 86 (1) ◽

pp. 85-91 ◽

Cited By ~ 1

Author(s):

Ayano Yokoi ◽

Yo Niida ◽

Mondo Kuroda ◽

Yoko Imi-Hashida ◽

Tomoko Toma ◽

...

Keyword(s):

B Cell ◽

Inclusion Bodies ◽

Class Ii ◽

Hla Class Ii ◽

Cell Disease ◽

Specific Accumulation ◽

Mucolipidosis Ii ◽

Hla Class Ii Molecules

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Identification of MAGE-3 Epitopes Presented by HLA-DR Molecules to CD4+ T Lymphocytes

Journal of Experimental Medicine ◽

10.1084/jem.189.5.767 ◽

1999 ◽

Vol 189 (5) ◽

pp. 767-778 ◽

Cited By ~ 170

Author(s):

Pascal Chaux ◽

Valérie Vantomme ◽

Vincent Stroobant ◽

Kris Thielemans ◽

Jurgen Corthals ◽

...

Keyword(s):

T Lymphocytes ◽

Tumor Antigens ◽

Class Ii ◽

Hla Class Ii ◽

Antigenic Peptides ◽

Recombinant Viruses ◽

Mhc Molecules ◽

Hla Dr ◽

Cell Clones ◽

Hla Class Ii Molecules

MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. We describe here the identification of the first MAGE-encoded epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules to CD4+ T lymphocytes. Monocyte-derived dendritic cells were loaded with a MAGE-3 recombinant protein and used to stimulate autologous CD4+ T cells. We isolated CD4+ T cell clones that recognized two different MAGE-3 epitopes, MAGE-3114–127 and MAGE-3121–134, both presented by the HLA-DR13 molecule, which is expressed in 20% of Caucasians. The second epitope is also encoded by MAGE-1, -2, and -6. Our procedure should be applicable to other proteins for the identification of new tumor-specific antigens presented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized with proteins or with recombinant viruses carrying entire genes coding for tumor antigens. The use of antigenic peptides presented by class II in addition to peptides presented by class I may also improve the efficacy of therapeutic antitumor vaccination.

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