title: Editorial

authors: Shieff, Sarah

abstract: This issue also presents new work from an unusual quarter, and in an unusual genre for JNZL. Ian Wedde's memoir 'A Little Bit Prickly...' was presented as the 9th annual Frank Sargeson Memorial Lecture at the University of Waikato on 15 September 2011. The English Programme of the University of Waikato has previously published the Sargeson lectures in its ephemeral Occasional Papers series, but we are now delighted to be able to offer these addresses a more permanent and accessible home in JNZL. Thanks indeed to Ian, New Zealand's poet laureate, for making his text available to us.

text: Editorial This issue also presents new work from an unusual quarter, and in an unusual genre for JNZL. Ian Wedde's memoir 'A Little Bit Prickly...' was presented as the 9th annual Frank Sargeson Memorial Lecture at the University of Waikato on 15 September 2011. The English Programme of the University of Waikato has previously published the Sargeson lectures in its ephemeral Occasional Papers series, but we are now delighted to be able to offer these addresses a more permanent and accessible home in JNZL. Thanks indeed to Ian, New Zealand's poet laureate, for making his text available to us.

year: 2011

title: The effects of allelic hinge variation in IgG3 antibodies on protein dynamics and effector functions

authors: Kuplich Barcellos, Marina

abstract: Antibodies play a crucial role in eliminating infections by recognising foreign antigens with high specificity and affinity. If a target is not directly neutralised, antibodies can mediate potent effector function responses by coordinating the recruitment of immune cells through their constant regions. These powerful immune functions are being widely explored in the form of IgG-based monoclonal antibody therapies for the treatment of infections, cancer, and autoimmune diseases. However, the antibody constant region exhibits significant genetic polymorphism, and new variants are rapidly being discovered by advances in genomic sequencing techniques. The documented effects of this diversity include differences in structural dynamics, thermal stability, and Fc-mediated effector functions among a number of antibody subclasses, including IgG1, IgG2, and IgG3. Some variants are reported to be a contributing factor to variability in the outcome of disease and responsiveness to vaccines in humans. The IgG3 subclass, in particular, displays striking differences in the antibody hinge region – responsible for connecting target binding with constant-region-mediated immune function. Here, exon duplications mean the hinge region can vary by as many as 45 amino acids in length. This work seeks to better understand some of the functional consequences of this unusual IgG3 variation. 

To assess the effects of allelic hinge variation on protein dynamics and effector functions, we have expressed a panel of seven anti-CD20 antibodies with unique constant region allele sequences from subclasses IgG1, IgG2, and IgG3. Sequence verified plasmids were used to express full-length antibodies in HEK293 cells at high purity. We first used small angle X-ray scattering (SAXS) to assess the variability in size and structural flexibility between the allelic variants and compared our data with previous research on the same variant panel with antiHER2 variable domain sequences. Following this structural analysis, we next undertook ADCC (antibody-dependent cellular cytotoxicity) and ADCP (antibody dependent cellular phagocytosis) assays to determine if differences in structural dynamics between the polymorphic variants could be linked to differences in effector function. These assays specifically used genome-engineered reporter cell lines to evaluate the ability of allelic variants to engage constant region binding FcyRIIIa and FcyRIIa Fc receptors, typically found on peripheral blood mononuclear cells. Activation was measured by quantifying the levels of luciferase expressed as a reporter.  

The findings provided in this study demonstrate that allelic variants with longer hinges have larger and more flexible structures and tend to present weaker ADCC and ADCP responses. The data presented here is the basis for future work on the influence of IgG constant region diversity on antibody structural dynamics and effector functions, which could contribute to improvements in the design of therapeutic antibodies.

text: The effects of allelic hinge variation in IgG3 antibodies on protein dynamics and effector functions Antibodies play a crucial role in eliminating infections by recognising foreign antigens with high specificity and affinity. If a target is not directly neutralised, antibodies can mediate potent effector function responses by coordinating the recruitment of immune cells through their constant regions. These powerful immune functions are being widely explored in the form of IgG-based monoclonal antibody therapies for the treatment of infections, cancer, and autoimmune diseases. However, the antibody constant region exhibits significant genetic polymorphism, and new variants are rapidly being discovered by advances in genomic sequencing techniques. The documented effects of this diversity include differences in structural dynamics, thermal stability, and Fc-mediated effector functions among a number of antibody subclasses, including IgG1, IgG2, and IgG3. Some variants are reported to be a contributing factor to variability in the outcome of disease and responsiveness to vaccines in humans. The IgG3 subclass, in particular, displays striking differences in the antibody hinge region – responsible for connecting target binding with constant-region-mediated immune function. Here, exon duplications mean the hinge region can vary by as many as 45 amino acids in length. This work seeks to better understand some of the functional consequences of this unusual IgG3 variation. 

To assess the effects of allelic hinge variation on protein dynamics and effector functions, we have expressed a panel of seven anti-CD20 antibodies with unique constant region allele sequences from subclasses IgG1, IgG2, and IgG3. Sequence verified plasmids were used to express full-length antibodies in HEK293 cells at high purity. We first used small angle X-ray scattering (SAXS) to assess the variability in size and structural flexibility between the allelic variants and compared our data with previous research on the same variant panel with antiHER2 variable domain sequences. Following this structural analysis, we next undertook ADCC (antibody-dependent cellular cytotoxicity) and ADCP (antibody dependent cellular phagocytosis) assays to determine if differences in structural dynamics between the polymorphic variants could be linked to differences in effector function. These assays specifically used genome-engineered reporter cell lines to evaluate the ability of allelic variants to engage constant region binding FcyRIIIa and FcyRIIa Fc receptors, typically found on peripheral blood mononuclear cells. Activation was measured by quantifying the levels of luciferase expressed as a reporter.  

The findings provided in this study demonstrate that allelic variants with longer hinges have larger and more flexible structures and tend to present weaker ADCC and ADCP responses. The data presented here is the basis for future work on the influence of IgG constant region diversity on antibody structural dynamics and effector functions, which could contribute to improvements in the design of therapeutic antibodies.

year: 2024

title: Faith, politics and reconciliation: the Roman Catholic Church, New Zealand Maori and indigenous Australians

authors: O'Sullivan, Dominic

abstract: The Roman Catholic Church claims from Jesus Christ a mission to teach consistently religious ideals in accordance with its understanding of God’s constant truth. These ideals include the belief that human creation in the image and likeness of God establishes rights to dignity, to culture, to religious freedom, to self-determination and a share in the common good. These ideals form the basis of the unique contribution to human affairs which the Church claims it can make. Although these are religious goals for the Church, they require political realisation, which means that the Church cannot but be alert to the formation of alliances of common intellectual aspiration around concrete political issues so that secular expression and context can be given to the magisterium (the Church’s body of teaching). At the same time the Catholic hierarchy is conscious of a need for caution in how it responds to political events lest that religious mission be compromised by a perception of it as a partisan political lobby group, thus lessening its capacity to make its unique contribution to human affairs. 

The Second Vatican Council reaffirmed that the Church’s religious objectives do not exist in isolation from the political order because human law, which is developed through the secular political process, should conform to the religious natural law. Prior to the Council’s reaffirmation the Australian and New Zealand Churches generally, but not exclusively, understated or misunderstood this relationship and became impotent in challenging secular objectives inconsistent with religious aspiration. In contrast when the Church has accepted the relationship, as it has since the Second Vatican Council, it has positioned itself to identify opportunities to give secular context and expression to religious thought. Such opportunities increased from the 1960s onwards as political developments in both Australia and New Zealand saw a secular questioning of racism and a broadening of the parameters of secular political debate to the extent that established Catholic thought was shifted from the fringes to the widening mainstream of public opinion on indigenous policy. 

Although the Second Vatican Council required attention to the relationship between religious ends and political means, the changing secular environment was a significant factor in encouraging public advocacy in support of indigenous aspiration, which peaked in Australia in the 1990s with substantial Church interest in the native title debate and with the Church playing a leading role in the entrenchment of reconciliation - a religious concept - on the Australian political landscape. In New Zealand there has been an equal but less vocal interest in reconciliation because the political process itself established the Treaty of Waitangi as a political context for reconciliation and a context around which the Church has been able to focus its interest in the advancement of Maori aspiration. Yet, while the Treaty of Waitangi and the associated bicultural discourse have provided contexts for the expression of religious principle, they have also detracted from the Church’s use of its own magisterium as the moral authority for the articulation of its aspirations for Maori.

text: Faith, politics and reconciliation: the Roman Catholic Church, New Zealand Maori and indigenous Australians The Roman Catholic Church claims from Jesus Christ a mission to teach consistently religious ideals in accordance with its understanding of God’s constant truth. These ideals include the belief that human creation in the image and likeness of God establishes rights to dignity, to culture, to religious freedom, to self-determination and a share in the common good. These ideals form the basis of the unique contribution to human affairs which the Church claims it can make. Although these are religious goals for the Church, they require political realisation, which means that the Church cannot but be alert to the formation of alliances of common intellectual aspiration around concrete political issues so that secular expression and context can be given to the magisterium (the Church’s body of teaching). At the same time the Catholic hierarchy is conscious of a need for caution in how it responds to political events lest that religious mission be compromised by a perception of it as a partisan political lobby group, thus lessening its capacity to make its unique contribution to human affairs. 

The Second Vatican Council reaffirmed that the Church’s religious objectives do not exist in isolation from the political order because human law, which is developed through the secular political process, should conform to the religious natural law. Prior to the Council’s reaffirmation the Australian and New Zealand Churches generally, but not exclusively, understated or misunderstood this relationship and became impotent in challenging secular objectives inconsistent with religious aspiration. In contrast when the Church has accepted the relationship, as it has since the Second Vatican Council, it has positioned itself to identify opportunities to give secular context and expression to religious thought. Such opportunities increased from the 1960s onwards as political developments in both Australia and New Zealand saw a secular questioning of racism and a broadening of the parameters of secular political debate to the extent that established Catholic thought was shifted from the fringes to the widening mainstream of public opinion on indigenous policy. 

Although the Second Vatican Council required attention to the relationship between religious ends and political means, the changing secular environment was a significant factor in encouraging public advocacy in support of indigenous aspiration, which peaked in Australia in the 1990s with substantial Church interest in the native title debate and with the Church playing a leading role in the entrenchment of reconciliation - a religious concept - on the Australian political landscape. In New Zealand there has been an equal but less vocal interest in reconciliation because the political process itself established the Treaty of Waitangi as a political context for reconciliation and a context around which the Church has been able to focus its interest in the advancement of Maori aspiration. Yet, while the Treaty of Waitangi and the associated bicultural discourse have provided contexts for the expression of religious principle, they have also detracted from the Church’s use of its own magisterium as the moral authority for the articulation of its aspirations for Maori.

year: 2003