A Family of Nonclassical Class I MHC Genes Contributes to Ultrasensitive Chemodetection by Mouse Vomeronasal Sensory Neurons

Moloney murine leukemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MSV) exert a regulatory effect on the class I genes of the murine major histocompatibility complex (MHC). We have previously shown that M-MuLV infection of mouse fibroblasts results in a substantial increase in cell surface expression of H-2K, H-2D, and H-2L proteins, whereas M-MSV, upon coinfection of the same cells, is apparently able to override the MuLV-induced increase in H-2 expression. As a result of this modulation, immune recognition of the infected cells is profoundly altered. Our efforts have been directed toward elucidating the molecular basis for this phenomenon. We report here that stimulation of interferon production as a result of infection with MuLV does not occur and, therefore, is not the cause of MuLV-induced enhancement of MHC expression. Control of H-2 class I and beta 2-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels. Our demonstration that M-MuLV controls expression of widely separated endogenous cellular genes (those coding for H-2D, H-2K, H-2L, and beta 2-microglobulin), transfected class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to sequences encoding a procaryotic enzyme, chloramphenicol acetyltransferase, suggests that M-MuLV exerts its effect in trans and not by proviral integration in the vicinity of the H-2 gene complex. Finally, we show that the sequences of at least one MHC gene, which are responsive to trans regulation by M-MuLV, lie within 1.2 kilobases upstream of the initiation codon for that gene.

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Susceptibility to murine lymphocytic choriomeningitis maps to class I MHC genes—a model for MHC/disease associations

Nature ◽

10.1038/316814a0 ◽

1985 ◽

Vol 316 (6031) ◽

pp. 814-817 ◽

Cited By ~ 53

Author(s):

R. M. Zinkernagel ◽

C. J. Pfau ◽

H. Hengartner ◽

A. Althage

Keyword(s):

Lymphocytic Choriomeningitis ◽

Class I ◽

Class I Mhc ◽

Mhc Genes ◽

Disease Associations

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Comparison of exon 5 sequences from 35 class I genes of the BALB/c mouse.

Journal of Experimental Medicine ◽

10.1084/jem.170.6.1837 ◽

1989 ◽

Vol 170 (6) ◽

pp. 1837-1858 ◽

Cited By ~ 16

Author(s):

K A Brorson ◽

S W Hunt ◽

T Hunkapiller ◽

Y H Sun ◽

H Cheroutre ◽

...

Keyword(s):

Dna Sequences ◽

Transmembrane Domain ◽

Sequence Similarity ◽

Class I ◽

Class I Mhc ◽

Mhc Genes ◽

Extensive Variation ◽

Sequences Analysis ◽

Transplantation Antigens ◽

Membrane Anchoring

DNA sequences of the fifth exon, which encodes the transmembrane domain, were determined for the BALB/c mouse class I MHC genes and used to study the relationships between them. Based on nucleotide sequence similarity, the exon 5 sequences can be divided into seven groups. Although most members within each group are at least 80% similar to each other, comparison between groups reveals that the groups share little similarity. However, in spite of the extensive variation of the fifth exon sequences, analysis of their predicted amino acid translations reveals that only four class I gene fifth exons have frameshifts or stop codons that terminate their translation and prevent them from encoding a domain that is both hydrophobic and long enough to span a lipid bilayer. Exactly 27 of the remaining fifth exons could encode a domain that is similar to those of the transplantation antigens in that it consists of a proline-rich connecting peptide, a transmembrane segment, and a cytoplasmic portion with membrane-anchoring basic residues. The conservation of this motif in the majority of the fifth exon translations in spite of extensive variation suggests that selective pressure exists for these exons to maintain their ability to encode a functional transmembrane domain, raising the possibility that many of the nonclassical class I genes encode functionally important products.

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Murine retroviruses control class I major histocompatibility antigen gene expression via a trans effect at the transcriptional level.

Molecular and Cellular Biology ◽

10.1128/mcb.7.7.2406 ◽

1987 ◽

Vol 7 (7) ◽

pp. 2406-2415 ◽

Cited By ~ 20

Author(s):

L D Wilson ◽

D C Flyer ◽

D V Faller

Keyword(s):

Gene Expression ◽

Class I ◽

Transcriptional Level ◽

Immune Recognition ◽

Mrna Levels ◽

Major Histocompatibility ◽

Class I Mhc ◽

Mhc Genes ◽

Beta 2 ◽

Beta 2 Microglobulin

Moloney murine leukemia virus (M-MuLV) and Moloney murine sarcoma virus (M-MSV) exert a regulatory effect on the class I genes of the murine major histocompatibility complex (MHC). We have previously shown that M-MuLV infection of mouse fibroblasts results in a substantial increase in cell surface expression of H-2K, H-2D, and H-2L proteins, whereas M-MSV, upon coinfection of the same cells, is apparently able to override the MuLV-induced increase in H-2 expression. As a result of this modulation, immune recognition of the infected cells is profoundly altered. Our efforts have been directed toward elucidating the molecular basis for this phenomenon. We report here that stimulation of interferon production as a result of infection with MuLV does not occur and, therefore, is not the cause of MuLV-induced enhancement of MHC expression. Control of H-2 class I and beta 2-microglobulin gene expression by M-MuLV, and probably by M-MSV, takes place at the transcriptional level as indicated by nuclear runoff studies and analysis of steady-state mRNA levels. Our demonstration that M-MuLV controls expression of widely separated endogenous cellular genes (those coding for H-2D, H-2K, H-2L, and beta 2-microglobulin), transfected class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to sequences encoding a procaryotic enzyme, chloramphenicol acetyltransferase, suggests that M-MuLV exerts its effect in trans and not by proviral integration in the vicinity of the H-2 gene complex. Finally, we show that the sequences of at least one MHC gene, which are responsive to trans regulation by M-MuLV, lie within 1.2 kilobases upstream of the initiation codon for that gene.

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