Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family.
B7-H4 is a recently identified B7 family member that negatively regulates T cell immunity by the inhibition of T cell proliferation, cytokine production, and cell cycle progression. In this study, we report that the genomic DNA of human B7-H4 is mapped on chromosome 1 comprised of six exons and five introns spanning 66 kb, of which exon 6 is used for alternative splicing to generate two different transcripts. Similar B7-H4 structure is also found in mouse genomic DNA in chromosome 3. A human B7-H4 pseudogene is identified in chromosome 20p11.1 with a single exon and two stop codons in the coding region. Immunohistochemistry analysis using B7-H4-specific mAb demonstrates that B7-H4 is not expressed on the majority of normal human tissues. In contrast, up to 85% (22 of 26) of ovarian cancer and 31% (5 of 16) of lung cancer tissues constitutively express B7-H4. Our results indicate a tight regulation of B7-H4 expression in the translational level in normal peripheral tissues and a potential role of B7-H4 in the evasion of tumor immunity.
Choi
In-Hak
IH
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.
Zhu
Gefeng
G
Sica
Gabriel L
GL
Strome
Scott E
SE
Cheville
John C
JC
Lau
Julie S
JS
Zhu
Yuwen
Y
Flies
Dallas B
DB
Tamada
Koji
K
Chen
Lieping
L
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005091:Exons / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D023061:Gene Order / Q000276:immunology; D006801:Humans; D007438:Introns / Q000235:genetics; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D051379:Mice; D005810:Multigene Family / Q000276:immunology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA / Q000379:methods; D014158:Transcription, Genetic / Q000276:immunology; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D018122:B7-1 Antigen; D009363:Neoplasm Proteins; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; C475824:Vtcn1 protein, mouse