The RAG cell line defines a new complementation group of MHC class II deficiency.
We previously described RAG, a mouse adenocarcinoma cell line, as deficient for the induction of major histocompatibility (MHC) class II antigens by IFN-gamma, but responding normally for MHC class I antigen stimulation and anti-viral protection. We had established that the fusion of RAG with various human cell lines restored the induction of MHC class II antigens, whenever the human chromosome 16 was present in somatic cell hybrids. Here we show that the RAG cell line does not exhibit any induction by IFN-gamma of DMA, DMB, and the invariant chain (Ii) mRNAs, and that the induction is restored in somatic cell hybrids containing human chromosome 16. In order to define the gene (designated F16) affected in the RAG cells, we performed a complementation analysis by fusing RAG with previously described human cell lines defective for MHC class II antigen expression (e.g., BLS cell lines), and which belong to five different complementation groups. Our data show that the resulting somatic cell hybrids present an inducible expression of mouse MHC class II antigens, Ii, DMA, and DMB. Therefore, the RAG cell line represents a yet undescribed cellular mutant affected in the expression of MHC class II antigens. In addition, we demonstrate that MHC class II antigens can be constitutively expressed in the RAG cell line when transfected with the cDNA encoding human CIITA driven by the RSV LTR promoter. Since the complementation analysis assessed that F16 and CIITA are distinct, our data suggest that F16 is required for the expression of CIITA.
Lennon
A
A
Unité d'Immunogénétique Humaine, INSERM, Institut Pasteur, Paris, France.
Ottone
C
C
Peijnenburg
A
A
Hamon-Benais
C
C
Colland
F
F
Gobin
S
S
van den Elsen
P
P
Fellous
M
M
Bono
R
R
Alcaïde-Loridan
C
C
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D002460:Cell Line; D015870:Gene Expression; D005802:Genes, MHC Class II; D005816:Genetic Complementation Test; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C045084:invariant chain; D007371:Interferon-gamma