KIR3DL1 is a highly polymorphic inhibitory Killer cell Immunoglobulin-like (KIR) Receptor gene wi... more KIR3DL1 is a highly polymorphic inhibitory Killer cell Immunoglobulin-like (KIR) Receptor gene with at least 23 alleles described, including its activating counterpart KIR3DS1. Recently, the KIR3DS1 allele has been shown to slow progression to AIDS in HLABw4*80I individuals. However, due to the lack of specific anti-KIR3DS1 antibody, expression and function have never been reported. In a study of 64 donors, we demonstrate KIR3DS1 expression on a substantial subset of peripheral Natural Killer (NK) cells through its recognition by the monoclonal antibody Z27. The fidelity of this detection method was confirmed by analysis of KIR3DS1 transfectants and the identification of a novel KIR3DS1 null allele. Furthermore, we show that ligation of KIR3DS1 by Z27 leads to NK cell degranulation and interferon gamma secretion. Finally, we document the persistence of KIR3DS1+ NK cells in HIV1 viremic patients. In conclusion, the high frequency of KIR3DS1 expression, together with its ability to ac...
The Killer cell Immunoglobulin-like Receptor (KIR) family of NK receptors contains both activatin... more The Killer cell Immunoglobulin-like Receptor (KIR) family of NK receptors contains both activating (e.g. 3DS1) and inhibitory (e.g. 3DL1) members. Unlike 3DL1, for which binding to HLA-Bw4 has been characterized, direct binding of HLA to 3DS1 has not been observed. However both genetic studies and in vitro viral replication assays suggest that this interaction can occur and is important in the context of viral infection. 3DL1 and 3DS1 are very similar in the region predicted to interact with HLA, suggesting the subtle differences translate into dramatic functional consequences. Modeling suggests four key differences in the D1 and D2 domains likely to affect interactions with Bw4. Single substitutions in this region dramatically reduced binding by 3DL1, suggesting that any of these changes would result in a lack of binding by 3DS1. In the reciprocal experiment however, we found that reversion of single amino acid residue - position 138 (W to G) was sufficient to confer HLA-Bw4 bindin...
Hepatitis C virus (HCV) binding to hepatocytes is thought to be mediated via interaction of the E... more Hepatitis C virus (HCV) binding to hepatocytes is thought to be mediated via interaction of the E2 glycoprotein with (co-)receptors including CD81 and scavenger receptor class B type I (SR-BI). Here, the expression of CD81 and SR-BI was analysed on peripheral blood mononuclear cell (PBMC) subsets, and the binding of genotype 1 soluble truncated E2 (sE2) proteins to these cells was investigated. All PBMC subsets expressed CD81, although at varying levels. In contrast, SR-BI was only detected on monocytes and dendritic cells (DCs). The genotype 1a H77c sE2 protein showed higher PBMC binding than other genotype 1a/b sE2s. H77c sE2 binding to different PBMC subsets largely paralleled their level of CD81 expression, and could be inhibited by blocking E2–CD81 interaction. However, those PBMC subsets reported to be infected by HCV in vivo (monocytes, DCs and B cells) also exhibited residual, CD81-independent binding, indicating roles for SR-BI/other receptor(s) in mediating haematopoietic ...
ABSTRACT Introduction Pneumococcal diseases are common and cause significant morbidity and mortal... more ABSTRACT Introduction Pneumococcal diseases are common and cause significant morbidity and mortality, with higher rates especially in developing areas including many in the Asia-Pacific (AP) region. However, current strategies to prevent pneumococcal disease in adults are quite complicated and not well implemented among many AP areas, and vaccination coverage rates among adults are generally low or perceived as low in the region. Thus, this literature review’s purpose was to summarize the disease burden and vaccination against pneumococcal diseases among adults in select AP areas (Australia, Hong Kong, India, Indonesia, South Korea, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). Areas Covered This systematic review included published articles from January 2010 to August 2020 using MEDLINE/Embase. Grey literature websites were searched for national immunization programs and medical society vaccination recommendations from areas of interest. A total of 69 publications were identified. Expert Opinion In the AP region, pneumococcal disease burden and serotype prevalence are variable among adult populations, particularly among older adults. Data was provided primarily from countries with established national immunization programs (NIPs). Further research on the disease burden and emphasis on the benefits of vaccination in AP areas lacking pneumococcal vaccination programs is warranted.
NK cell activity is regulated by the integration of positive and negative signals. One important ... more NK cell activity is regulated by the integration of positive and negative signals. One important source of these signals for human NK cells is the killer Ig-like receptor (KIR) family, which includes both members that transduce positive and those that generate negative signals. KIR3DL1 inhibits NK cell activity upon engagement by its ligand HLA-Bw4. The highly homologous KIR3DS1 is an activating receptor, which is implicated in the outcome of a variety of pathological situations. However, unlike KIR3DL1, direct binding of KIR3DS1+ cells to HLA has not been demonstrated. We analyzed four key amino acid differences between KIR3DL1*01502 and KIR3DS1*013 to determine their role in KIR binding to HLA. Single substitutions of these residues dramatically reduced binding by KIR3DL1. In the reciprocal experiment, we found that the rare KIR3DS1 allotype KIR3DS1*014 binds HLA-Bw4 even though it differs from KIR3DS1*013 at only one of these positions (position 138). This reactivity was unexpect...
Natural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA... more Natural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA) binding to sialic acid (SA) on activating NK receptors. SA also acts as a receptor for the binding of influenza virus to its target host cells. The SA binding properties of H3N2 influenza viruses have been observed to change during circulation in humans: recent isolates are unable to agglutinate chicken red blood cells and show reduced affinity for synthetic glycopolymers representing SA-␣-2,3-lactose (3SL-PAA) and SA-␣-2,6-N-acetyl lactosamine (6SLN-PAA) carbohydrates. Here, NK lysis of cells infected with human H3N2 influenza viruses isolated between 1969 and 2003 was analyzed. Cells infected with recent isolates (1999 to 2003) were found to be lysed less effectively than cells infected with older isolates (1969 to 1996). This change occurred concurrently with the acquisition of two new potential glycosylation site motifs in HA. Deletion of the potential glycosylation site motif at 133 to 135 in HA1 from a recent isolate partially restored the agglutination phenotype to a recombinant virus, indicating that the HA-SA interaction is inhibited by the glycosylation modification. Deletion of either of the recently acquired potential glycosylation sites from HA led to increased NK lysis of cells infected with recombinant viruses carrying modified HA. These results indicate that alterations in HA glycosylation may affect NK cell recognition of influenza virus-infected cells in addition to virus binding to host cells.
The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies ... more The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies and is presently being evaluated as an HCV vaccine candidate. HCV binds to human cells through the interaction of E2 with the tetraspanin CD81, a putative viral receptor component. We have analyzed four different E2 proteins from 1a and 1b viral isolates for their ability to bind to recombinant CD81 in vitro and to the native receptor displayed on the surface of Molt-4 cells. A substantial difference in binding efficiency between these E2 variants was observed, with proteins derived from 1b subtypes showing significantly lower binding than the 1a protein. To elucidate the mechanism of E2-CD81 interaction and to identify critical regions responsible for the different binding efficiencies of the E2 variants, several mutants were generated in E2 protein regions predicted by computer modeling to be exposed on the protein surface. Functional analysis of these E2 derivatives revealed that at l...
KIR3DL1 shows extensive polymorphism, and its variation has functional significance in terms of c... more KIR3DL1 shows extensive polymorphism, and its variation has functional significance in terms of cell-surface expression levels and inhibitory capacity. We characterized nine KIR3DL1 alleles (*022, *028, *029, *033, *035, *051, *052, *053, and *054), four of which were identified ...
KIR3DL1 is a highly polymorphic killer cell Ig-like receptor gene with at least 23 alleles descri... more KIR3DL1 is a highly polymorphic killer cell Ig-like receptor gene with at least 23 alleles described, including its activating counterpart, KIR3DS1. Recently, the KIR3DS1 allele has been shown to slow progression to AIDS in individuals expressing HLA-Bw4 with isoleucine at position 80. However, due to the lack of a specific Ab, KIR3DS1 expression and function is not well characterized. In this study, we demonstrate KIR3DS1 expression on a substantial subset of peripheral natural killer cells through its recognition by the mAb Z27. The fidelity of this detection method was confirmed by analysis of KIR3DS1 transfectants and the identification of a novel KIR3DS1 null allele. Interestingly, KIR3DS1 is also expressed by a small proportion of CD56 ؉ T cells. We show that ligation of KIR3DS1 by Z27 leads to NK cell IFN-␥ production and degranulation as assessed by expression of CD107a. Furthermore, we document the persistence of KIR3DS1 ؉ NK cells in HIV-1 viremic patients. The high frequency of KIR3DS1 expression, along with its ability to activate NK cells, and its maintenance during HIV-1 viremia are consistent with the epidemiological data suggesting a critical role for this receptor in controlling HIV-1 pathogenesis.
Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patter... more Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 ...
KIR3DL1 is a highly polymorphic inhibitory Killer cell Immunoglobulin-like (KIR) Receptor gene wi... more KIR3DL1 is a highly polymorphic inhibitory Killer cell Immunoglobulin-like (KIR) Receptor gene with at least 23 alleles described, including its activating counterpart KIR3DS1. Recently, the KIR3DS1 allele has been shown to slow progression to AIDS in HLABw4*80I individuals. However, due to the lack of specific anti-KIR3DS1 antibody, expression and function have never been reported. In a study of 64 donors, we demonstrate KIR3DS1 expression on a substantial subset of peripheral Natural Killer (NK) cells through its recognition by the monoclonal antibody Z27. The fidelity of this detection method was confirmed by analysis of KIR3DS1 transfectants and the identification of a novel KIR3DS1 null allele. Furthermore, we show that ligation of KIR3DS1 by Z27 leads to NK cell degranulation and interferon gamma secretion. Finally, we document the persistence of KIR3DS1+ NK cells in HIV1 viremic patients. In conclusion, the high frequency of KIR3DS1 expression, together with its ability to ac...
The Killer cell Immunoglobulin-like Receptor (KIR) family of NK receptors contains both activatin... more The Killer cell Immunoglobulin-like Receptor (KIR) family of NK receptors contains both activating (e.g. 3DS1) and inhibitory (e.g. 3DL1) members. Unlike 3DL1, for which binding to HLA-Bw4 has been characterized, direct binding of HLA to 3DS1 has not been observed. However both genetic studies and in vitro viral replication assays suggest that this interaction can occur and is important in the context of viral infection. 3DL1 and 3DS1 are very similar in the region predicted to interact with HLA, suggesting the subtle differences translate into dramatic functional consequences. Modeling suggests four key differences in the D1 and D2 domains likely to affect interactions with Bw4. Single substitutions in this region dramatically reduced binding by 3DL1, suggesting that any of these changes would result in a lack of binding by 3DS1. In the reciprocal experiment however, we found that reversion of single amino acid residue - position 138 (W to G) was sufficient to confer HLA-Bw4 bindin...
Hepatitis C virus (HCV) binding to hepatocytes is thought to be mediated via interaction of the E... more Hepatitis C virus (HCV) binding to hepatocytes is thought to be mediated via interaction of the E2 glycoprotein with (co-)receptors including CD81 and scavenger receptor class B type I (SR-BI). Here, the expression of CD81 and SR-BI was analysed on peripheral blood mononuclear cell (PBMC) subsets, and the binding of genotype 1 soluble truncated E2 (sE2) proteins to these cells was investigated. All PBMC subsets expressed CD81, although at varying levels. In contrast, SR-BI was only detected on monocytes and dendritic cells (DCs). The genotype 1a H77c sE2 protein showed higher PBMC binding than other genotype 1a/b sE2s. H77c sE2 binding to different PBMC subsets largely paralleled their level of CD81 expression, and could be inhibited by blocking E2–CD81 interaction. However, those PBMC subsets reported to be infected by HCV in vivo (monocytes, DCs and B cells) also exhibited residual, CD81-independent binding, indicating roles for SR-BI/other receptor(s) in mediating haematopoietic ...
ABSTRACT Introduction Pneumococcal diseases are common and cause significant morbidity and mortal... more ABSTRACT Introduction Pneumococcal diseases are common and cause significant morbidity and mortality, with higher rates especially in developing areas including many in the Asia-Pacific (AP) region. However, current strategies to prevent pneumococcal disease in adults are quite complicated and not well implemented among many AP areas, and vaccination coverage rates among adults are generally low or perceived as low in the region. Thus, this literature review’s purpose was to summarize the disease burden and vaccination against pneumococcal diseases among adults in select AP areas (Australia, Hong Kong, India, Indonesia, South Korea, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). Areas Covered This systematic review included published articles from January 2010 to August 2020 using MEDLINE/Embase. Grey literature websites were searched for national immunization programs and medical society vaccination recommendations from areas of interest. A total of 69 publications were identified. Expert Opinion In the AP region, pneumococcal disease burden and serotype prevalence are variable among adult populations, particularly among older adults. Data was provided primarily from countries with established national immunization programs (NIPs). Further research on the disease burden and emphasis on the benefits of vaccination in AP areas lacking pneumococcal vaccination programs is warranted.
NK cell activity is regulated by the integration of positive and negative signals. One important ... more NK cell activity is regulated by the integration of positive and negative signals. One important source of these signals for human NK cells is the killer Ig-like receptor (KIR) family, which includes both members that transduce positive and those that generate negative signals. KIR3DL1 inhibits NK cell activity upon engagement by its ligand HLA-Bw4. The highly homologous KIR3DS1 is an activating receptor, which is implicated in the outcome of a variety of pathological situations. However, unlike KIR3DL1, direct binding of KIR3DS1+ cells to HLA has not been demonstrated. We analyzed four key amino acid differences between KIR3DL1*01502 and KIR3DS1*013 to determine their role in KIR binding to HLA. Single substitutions of these residues dramatically reduced binding by KIR3DL1. In the reciprocal experiment, we found that the rare KIR3DS1 allotype KIR3DS1*014 binds HLA-Bw4 even though it differs from KIR3DS1*013 at only one of these positions (position 138). This reactivity was unexpect...
Natural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA... more Natural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA) binding to sialic acid (SA) on activating NK receptors. SA also acts as a receptor for the binding of influenza virus to its target host cells. The SA binding properties of H3N2 influenza viruses have been observed to change during circulation in humans: recent isolates are unable to agglutinate chicken red blood cells and show reduced affinity for synthetic glycopolymers representing SA-␣-2,3-lactose (3SL-PAA) and SA-␣-2,6-N-acetyl lactosamine (6SLN-PAA) carbohydrates. Here, NK lysis of cells infected with human H3N2 influenza viruses isolated between 1969 and 2003 was analyzed. Cells infected with recent isolates (1999 to 2003) were found to be lysed less effectively than cells infected with older isolates (1969 to 1996). This change occurred concurrently with the acquisition of two new potential glycosylation site motifs in HA. Deletion of the potential glycosylation site motif at 133 to 135 in HA1 from a recent isolate partially restored the agglutination phenotype to a recombinant virus, indicating that the HA-SA interaction is inhibited by the glycosylation modification. Deletion of either of the recently acquired potential glycosylation sites from HA led to increased NK lysis of cells infected with recombinant viruses carrying modified HA. These results indicate that alterations in HA glycosylation may affect NK cell recognition of influenza virus-infected cells in addition to virus binding to host cells.
The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies ... more The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies and is presently being evaluated as an HCV vaccine candidate. HCV binds to human cells through the interaction of E2 with the tetraspanin CD81, a putative viral receptor component. We have analyzed four different E2 proteins from 1a and 1b viral isolates for their ability to bind to recombinant CD81 in vitro and to the native receptor displayed on the surface of Molt-4 cells. A substantial difference in binding efficiency between these E2 variants was observed, with proteins derived from 1b subtypes showing significantly lower binding than the 1a protein. To elucidate the mechanism of E2-CD81 interaction and to identify critical regions responsible for the different binding efficiencies of the E2 variants, several mutants were generated in E2 protein regions predicted by computer modeling to be exposed on the protein surface. Functional analysis of these E2 derivatives revealed that at l...
KIR3DL1 shows extensive polymorphism, and its variation has functional significance in terms of c... more KIR3DL1 shows extensive polymorphism, and its variation has functional significance in terms of cell-surface expression levels and inhibitory capacity. We characterized nine KIR3DL1 alleles (*022, *028, *029, *033, *035, *051, *052, *053, and *054), four of which were identified ...
KIR3DL1 is a highly polymorphic killer cell Ig-like receptor gene with at least 23 alleles descri... more KIR3DL1 is a highly polymorphic killer cell Ig-like receptor gene with at least 23 alleles described, including its activating counterpart, KIR3DS1. Recently, the KIR3DS1 allele has been shown to slow progression to AIDS in individuals expressing HLA-Bw4 with isoleucine at position 80. However, due to the lack of a specific Ab, KIR3DS1 expression and function is not well characterized. In this study, we demonstrate KIR3DS1 expression on a substantial subset of peripheral natural killer cells through its recognition by the mAb Z27. The fidelity of this detection method was confirmed by analysis of KIR3DS1 transfectants and the identification of a novel KIR3DS1 null allele. Interestingly, KIR3DS1 is also expressed by a small proportion of CD56 ؉ T cells. We show that ligation of KIR3DS1 by Z27 leads to NK cell IFN-␥ production and degranulation as assessed by expression of CD107a. Furthermore, we document the persistence of KIR3DS1 ؉ NK cells in HIV-1 viremic patients. The high frequency of KIR3DS1 expression, along with its ability to activate NK cells, and its maintenance during HIV-1 viremia are consistent with the epidemiological data suggesting a critical role for this receptor in controlling HIV-1 pathogenesis.
Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patter... more Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 ...
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Papers by Eriko Yamada