HGNC Approved Gene Symbol:PDCD1LG2
Cytogenetic location:9p24.1 Genomic coordinates(GRCh38) :9:5,510,531-5,571,282 (from NCBI)
By searching EST databases with mouse Pd1 ligand-1 (Pdl1, or B7H1;605402),Latchman et al. (2001) identified cDNAs encoding mouse Pdl2 and human PDL2, which they cloned from a placenta cDNA library. Sequence analysis predicted that the 273-amino acid PDL2 protein, which is 70% identical to the mouse Pdl2 protein, contains a signal sequence, IgV- and IgC-like domains, a transmembrane region, and a cytoplasmic region. Northern blot analysis detected wide expression of PDL2, with highest levels in placenta, heart, pancreas, lung, and liver, and lower levels in spleen, lymph nodes, and thymus. Stimulation with gamma-interferon (IFNG;147570) was required to detect expression in monocytes.
By screening a subtractive dendritic cell (DC)-activated macrophage cDNA library,Tseng et al. (2001) isolated mouse and human cDNAs encoding PDL2, which they termed B7DC. Northern blot analysis detected Pdl2 transcripts in mouse DCs but not in primary macrophages or macrophage cell lines. Expression was also detected in human DCs but not in placenta.
Using flow cytometric analysis,Latchman et al. (2001) showed that the IgV region of mouse Pdl2, like Pdl1, binds to human PDCD1 (600244) but not to CTLA4 (123890), CD28 (186760), or ICOS (604558). Stimulation of mouse T cells with anti-CD3 (see186740) and Pdl2 or Pdl1 resulted in inhibition of proliferation and cytokine production, and Pdl2 could inhibit T-cell receptor (see186880)-CD28 signals at low antigen concentrations.Latchman et al. (2001) proposed that blocking of the PDL-PDCD1 pathway may enhance antitumor immunity, whereas stimulating this pathway may help downregulate graft rejection and autoimmune and allergic reactions.
Functional analysis byTseng et al. (2001) showed that, in the presence of low concentrations of anti-CD3, mouse Pdl2 preferentially costimulated CD4 (186940)-positive (Th1) T-cell proliferation and Ifng production to a greater level than did B7.1.
By analysis of a BAC clone (GenBankAL162253),Latchman et al. (2001) mapped the PDL2 gene to chromosome 9p24.2, in close proximity to the PDL1 gene.Tseng et al. (2001) mapped the mouse Pdl2 gene to chromosome 19C2-C3.
Matsumoto et al. (2004) investigated the roles of B7h1 and B7dc using a murine allergic asthma model. They found constitutive expression of B7h1 on DCs, macrophages, B cells, and T cells in lungs of naive animals. Expression of B7h1 increased dramatically after allergen challenge. In contrast, B7dc had low constitutive expression, with some upregulation on DCs after allergen challenge. Treatment of mice with anti-B7dc at the time of allergen challenge, but not at the time of sensitization, significantly increased airway hyperreactivity and eosinophilia in association with increased production of Il5 (147850) and Il13 (147683) and decreased production of Ifng. These changes were diminished in mice pretreated with anti-Ifng, but not with anti-B7h1 or anti-Pd1.Matsumoto et al. (2004) concluded that B7DC is involved in the regulation of the asthmatic response in an IFNG-dependent, PD1-independent manner.
Zhang et al. (2006) generated healthy and fertile Pdl2 -/- mice by deleting most of the second coding exon. Antigen-presenting cells from Pdl2 -/- mice induced stronger T-cell proliferation in vitro and in vivo compared with wildtype cells. In the presence of anti-Pd1, Pdl2 -/- and wildtype cells induced similar levels of T-cell proliferation, indicating that PDL2 might mediate negative regulation of T cells via PD1 engagement. Induction of tolerance to an oral antigen was abrogated in the absence of Pdl2.Zhang et al. (2006) concluded that PDL2 negatively regulates T cells and plays an essential role in immune tolerance.
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., Greenfield, E. A., Bourque, K.PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nature Immun. 2: 261-268, 2001. [PubMed:11224527,related citations] [Full Text]
Matsumoto, K., Inoue, H., Nakano, T., Tsuda, M., Yoshiura, Y., Fukuyama, S., Tsushima, F., Hoshino, T., Aizawa, H., Akiba, H., Pardoll, D., Hara, N., Yagita, H., Azuma, M., Nakanishi, Y.B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism. J. Immun. 172: 2530-2541, 2004. [PubMed:14764726,related citations] [Full Text]
Tseng, B. S.-Y., Otsuji, M., Gorski, K., Huang, X., Slansky, J. E., Pai, S. I., Shalabi, A., Shin, T., Pardoll, D. M., Tsuchiya, H.B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J. Exp. Med. 193: 839-845, 2001. [PubMed:11283156,images,related citations] [Full Text]
Zhang, Y., Chung, Y., Bishop, C., Daugherty, B., Chute, H., Holst, P., Kurahara, C., Lott, F., Sun, N., Welcher, A. A., Dong, C.Regulation of T cell activation and tolerance by PDL2. Proc. Nat. Acad. Sci. 103: 11695-11700, 2006. [PubMed:16864790,images,related citations] [Full Text]
Alternative titles; symbols
HGNC Approved Gene Symbol: PDCD1LG2
Cytogenetic location: 9p24.1 Genomic coordinates(GRCh38) : 9:5,510,531-5,571,282(from NCBI)
By searching EST databases with mouse Pd1 ligand-1 (Pdl1, or B7H1; 605402), Latchman et al. (2001) identified cDNAs encoding mouse Pdl2 and human PDL2, which they cloned from a placenta cDNA library. Sequence analysis predicted that the 273-amino acid PDL2 protein, which is 70% identical to the mouse Pdl2 protein, contains a signal sequence, IgV- and IgC-like domains, a transmembrane region, and a cytoplasmic region. Northern blot analysis detected wide expression of PDL2, with highest levels in placenta, heart, pancreas, lung, and liver, and lower levels in spleen, lymph nodes, and thymus. Stimulation with gamma-interferon (IFNG; 147570) was required to detect expression in monocytes.
By screening a subtractive dendritic cell (DC)-activated macrophage cDNA library, Tseng et al. (2001) isolated mouse and human cDNAs encoding PDL2, which they termed B7DC. Northern blot analysis detected Pdl2 transcripts in mouse DCs but not in primary macrophages or macrophage cell lines. Expression was also detected in human DCs but not in placenta.
Using flow cytometric analysis, Latchman et al. (2001) showed that the IgV region of mouse Pdl2, like Pdl1, binds to human PDCD1 (600244) but not to CTLA4 (123890), CD28 (186760), or ICOS (604558). Stimulation of mouse T cells with anti-CD3 (see 186740) and Pdl2 or Pdl1 resulted in inhibition of proliferation and cytokine production, and Pdl2 could inhibit T-cell receptor (see 186880)-CD28 signals at low antigen concentrations. Latchman et al. (2001) proposed that blocking of the PDL-PDCD1 pathway may enhance antitumor immunity, whereas stimulating this pathway may help downregulate graft rejection and autoimmune and allergic reactions.
Functional analysis by Tseng et al. (2001) showed that, in the presence of low concentrations of anti-CD3, mouse Pdl2 preferentially costimulated CD4 (186940)-positive (Th1) T-cell proliferation and Ifng production to a greater level than did B7.1.
By analysis of a BAC clone (GenBank AL162253), Latchman et al. (2001) mapped the PDL2 gene to chromosome 9p24.2, in close proximity to the PDL1 gene. Tseng et al. (2001) mapped the mouse Pdl2 gene to chromosome 19C2-C3.
Matsumoto et al. (2004) investigated the roles of B7h1 and B7dc using a murine allergic asthma model. They found constitutive expression of B7h1 on DCs, macrophages, B cells, and T cells in lungs of naive animals. Expression of B7h1 increased dramatically after allergen challenge. In contrast, B7dc had low constitutive expression, with some upregulation on DCs after allergen challenge. Treatment of mice with anti-B7dc at the time of allergen challenge, but not at the time of sensitization, significantly increased airway hyperreactivity and eosinophilia in association with increased production of Il5 (147850) and Il13 (147683) and decreased production of Ifng. These changes were diminished in mice pretreated with anti-Ifng, but not with anti-B7h1 or anti-Pd1. Matsumoto et al. (2004) concluded that B7DC is involved in the regulation of the asthmatic response in an IFNG-dependent, PD1-independent manner.
Zhang et al. (2006) generated healthy and fertile Pdl2 -/- mice by deleting most of the second coding exon. Antigen-presenting cells from Pdl2 -/- mice induced stronger T-cell proliferation in vitro and in vivo compared with wildtype cells. In the presence of anti-Pd1, Pdl2 -/- and wildtype cells induced similar levels of T-cell proliferation, indicating that PDL2 might mediate negative regulation of T cells via PD1 engagement. Induction of tolerance to an oral antigen was abrogated in the absence of Pdl2. Zhang et al. (2006) concluded that PDL2 negatively regulates T cells and plays an essential role in immune tolerance.
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., Greenfield, E. A., Bourque, K.PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nature Immun. 2: 261-268, 2001. [PubMed: 11224527] [Full Text: https://doi.org/10.1038/85330]
Matsumoto, K., Inoue, H., Nakano, T., Tsuda, M., Yoshiura, Y., Fukuyama, S., Tsushima, F., Hoshino, T., Aizawa, H., Akiba, H., Pardoll, D., Hara, N., Yagita, H., Azuma, M., Nakanishi, Y.B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism. J. Immun. 172: 2530-2541, 2004. [PubMed: 14764726] [Full Text: https://doi.org/10.4049/jimmunol.172.4.2530]
Tseng, B. S.-Y., Otsuji, M., Gorski, K., Huang, X., Slansky, J. E., Pai, S. I., Shalabi, A., Shin, T., Pardoll, D. M., Tsuchiya, H.B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J. Exp. Med. 193: 839-845, 2001. [PubMed: 11283156] [Full Text: https://doi.org/10.1084/jem.193.7.839]
Zhang, Y., Chung, Y., Bishop, C., Daugherty, B., Chute, H., Holst, P., Kurahara, C., Lott, F., Sun, N., Welcher, A. A., Dong, C.Regulation of T cell activation and tolerance by PDL2. Proc. Nat. Acad. Sci. 103: 11695-11700, 2006. [PubMed: 16864790] [Full Text: https://doi.org/10.1073/pnas.0601347103]
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